Today, we announce the winner of the vote. Dr. Qiang Chang’s proposal to study MECP2, a protein critical for Rett Syndrome, received over 15,000 votes and won the $10,000 cash prize. Runners up for the competition include Dr. Hans Bjornsson’s proposal for Kabuki Syndrome and Dr. Renee Sears’s proposal for Fahr’s disease. They will receive access to the Microryza crowdfunding platform for free. Second runners up include Dr. George Carlson’s proposal for Fatal Familial Insomnia, Dr. Beth Drolet’s proposal for PHACE Syndrome, and Dr. Stefan Stamm’s proposal for Prader Willi. They will receive access to the Microryza crowdfunding platform for half price.

Rare diseases affect more than 25 million Americans, yet less than five percent of the 7,000 known rare diseases have treatments available. The BeHEARD Challenge encourages non-profits, academic researchers, rare disease advocacy groups, families of rare disease patients and for-profit companies to collaborate in their collective mission to advance rare disease research.

About Rare Genomics Institute
RGI is a non-profit that makes cutting edge research technologies and experts accessible to rare disease patients. By providing an expert network and an online crowdfunding mechanism, RGI helps families source, design, and fund personalized research projects in diseases not otherwise studied. Ultimately, RGI aims to expand on its current genome sequencing-focused approach to enable community funding to support whatever type of research is necessary to get closer to rare disease therapeutics. For more information, visit: http://raregenomics.org/.

About Assay Depot
Assay Depot is the world’s leading provider of outsourced scientific services. The company operates a network of online research marketplaces that dramatically streamline purchases between scientists and 8,000+ global research vendors. Assay Depot is changing the way life science research is done. To learn more about Assay Depot’s enterprise software, visit http://enterprise.assaydepot.com. To use Assay Depot’s free public marketplace, visit http://www.assaydepot.com.

Written by Edbert Khong

Our first podcast with SWAN on 6/28/2012, with Amy Clugston of SWAN moderating and Jimmy Lin, Naira Rezende, and Marisa Dolled-Filhart as panelists about rare and undiagnosed diseases can be found here.

Our first podcast with Ben’s Friends on 10/4/12, featuring rare disease innovations and Ataxia. Panelists were Dr. Gholson, Dr. Angrist, and Dr. Perlman. The first hour is here and the bonus half hour about Ataxia is found here. Both can be seen on this site.

Our second podcast with Ben’s Friends on 12/6/12, featuring C. Elegans and Trigeminal Neuralgia, featured Doctors Golden, Stern, Cheshire, and Lawhern is here.

Our first podcast produced on our own features Mouse Models and Transverse Myelitis. Dr. Benjamin Greenberg, Dr. Allen Desena, and Dr. Cathleen Lutz will be joining us to talk about these topics on February 7th from 7-8:30 PM. Hope to see you there! RSVP here.

 A guest post written by Sama Boles.

The Rare99X Clinical Exome Challenge holds great potential to transform the way genome sequencing and exploration of rare diseases are currently being done by scientists and researchers.

WHO: Jimmy Lin, the founder of Rare Genomics Institute who received his MD/PhD from Johns Hopkins School of Medicine. He currently is a research instructor leading the clinical exome sequencing initiative in the Genomic & Pathology Services with Washington University in St. Louis.

WHEN: Partnering for Cures will be held November 28-30, 2012. The Rare99X Clinical Exome Challenge Presentation is scheduled for November 30th, from 10:15-10:40am.

WHERE: Grand Hyatt Hotel, New York City

BACKGROUND: Partnering for Cures brings together 800 leaders from all sectors of the medical research enterprise to speed up the time it takes to turn promising scientific discoveries into treatments. It is convened by FasterCures, a center of the Milken Institute.

In addition to the innovator presentations, the meeting features a stellar speaker line-up, including: NIH’s Francis Collins, FDA’s Janet Woodcock, QB3′s Regis Kelly, Arizona State University’s Anna Barker, Onyx Pharmaceuticals’ Anthony Coles, PureTech Ventures’ Ben Shapiro, the Michael J. Fox Foundation’s Todd Sherer, and many other leaders from industry, academia, finance, philanthropy, and government. Partnering for Cures also features a state-of-the-art partnering system that eases the process of networking and finding nontraditional allies.

For more information and to register, please visit www.partneringforcures.org.

For more information about RGI, contact:
Amanda Lordemann, Director of Media Relations. amanda.lordemann@raregenomics.org

For more information about Partnering for Cures and FasterCures, contact:
Cecilia Arradaza
Communications & Marketing Director, FasterCures
carradaza@fastercures.org

The report, Privacy and Progress in Whole Genome Sequencing contains recommendations on how the country should proceed along the genomic path and protect individual privacy and data security while, “leaving ample room for data sharing opportunities that propel scientific and medical progress.”

The PCSBI is an advisory panel of the nation’s leaders in medicine, science, ethics, religion, law, and engineering. The Commission advises the President of the United Stats on bioethical issues arising from advances in biomedicine and related areas of science and technology. The Commission seeks to identify and promote policies and practices that ensure scientific research, health care delivery, and technological innovation are conducted in a socially and ethically responsible manner.

To view the Commission’s press release go to: http://www.bioethics.gov/cms/node/765

To view the PCSBI website: http://bioethics.gov

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Jimmy:                    Hello everyone and welcome to this session of our podcast series that we’ve created. The purpose of this podcast is to enable open access from the general community to top research experts and health experts so that everybody can have their questions answered. We did our first podcasts between Rare Genomics Institute and SWAN, that happened a while back and we are starting a new series between the Rare Genomics Institute and Ben’s Friends. My name is Jimmy Lin, I am the president of Rare Genomics Institute and co-hosting with me is Ben from Ben’s Friends and John from Ben’s Friends. Would you like to introduce yourself and introduce a little bit about the Ben’s Friends?

Ben:                        Yeah, sure! Hello everybody, this is Ben. Hello and welcome to the first installment of podcast series sponsored   by Ben’s Friends and Rare genomics. For those of you who are unfamiliar with Ben’s Friends, our mission is to ensure that everybody in the world who has a rare disease can stick together and connect with others like them. Ben’s Friends creates online support communities for folks with rare diseases and out of thirty three rare diseases, with over twenty three thousand members and over a five hundred thousand page views a month. We’ve already doubled the traffic once this year and one of those rare diseases is ataxia. For more information, visit www.bensfriends.org. So now, I’m going to turn to John who will describe how the hour will go.

John:                      Alright, the first half hour we’re going to discuss the exciting technology impacting rare diseases. Our main focus will be whole exome and whole genome sequencing. In the second half hour we will feature a particular disease and in today’s segment, we’ll focus on ataxia. At the end of each segment, we’ll be answering your live questions which you can post on our facebook page. This podcast is an opportunity for the general community to engage the experts who will provide the true mechanisms for the listeners to ask questions. Anytime during our conversation go to the RGI’s facebook page which is www.facebook.com/raregenomics and comment on the post with your questions. I’m turning back to Jimmy who will introduce the experts to start the talk about the newest technologies for rare disease research.

Jimmy:                    Thanks John. A quick disclaimer before we start. We’re sharing a lot of state of the art and new information. This is just for educational purposes. This is not to replace talking to your doctor. So if you have any specific questions, make sure you do talk to your doctor and this hopefully will be a helpful resource just for educational purposes. And just also for a quick introduction about Rare Genomics Institute, we are a voluntary organization that has been started to help patients with rare diseases access top researchers and fund their research using crowd funding. Right now the methods we are using are genome sequencing as we’re helping patients to do that and we had our first few discoveries in the last month, and we’re hoping to use other technologies and fund other technologies to help understand what these sequences mean. This is an exciting development. We’re excited also to partner with top experts and to bring this to the general public.

Today, the first half, like John mentioned, we are going to talk about one of the  technologies that have been developing in the life sciences base and for us, we have two experts, Dr. Gholson Lyon, Dr. Misha Angrist.

Dr. Ghoslon Lyon is the Assistant Professor at the Human Genetics at Cold Spring Harbor Laboratory and also a researcher at the Utah Foundation for Biomedical Research. He’s a board-certified child, adolescent and adult psychiatrist. His focus is on the on the genetic basis of rare Mendelian diseases and the development of clinical-grade exome and whole genome sequencing. Welcome!

Dr. Lyon:                Great thanks for having me.

Jimmy:                    Our second guest today is Dr. Misha Angrist. Dr. Angrist is an Assistant Professor at Duke University’s Institute for Genome Sciences & Policy and he teaches genetics as well as ethical and legal and social implications of genetics. He did his doctoral work at Case Western and very interesting, also has an MFA in writing and literature. He had training before as a genetic councilor and another interesting thing is that he was the fourth participant at the PGP, the Personal Genome Project. So he had his entire genome sequenced twice and it’s now public so you can actually access Dr. Angrist’s genome online. He wrote about in the book called ‘The Human Being: At the Dawn of Personal Genomics’. Currently, he’s a great advocate in patient’s advocacy  – helping patients in undergoing research studies being able figure out and to learn more about the results. And currently, he’s a Co-Principal Investigator of Duke’s Task Force for Neonatal Genomics. So, welcome Misha.

Dr. Angrist:            Thanks so much for having me!

Jimmy:                    It’s been a really cool time in biology and maybe we can start off asking Misha why there is such an excitement on sequencing? What’s the big deal? Why are people always talking about it these days?

Dr. Angrist:            Well, the short answer is ‘money’. It has become less expensive now to look at the whole genome, or the whole exome, that is the part of the genome that codes for protein, about 2% of the total human DNA. So what that means is that patients who used to be destined to go on what we call a long diagnostic odyssey. That is the test after test, the strong suspicion. This is particularly true for people with rare conditions and there would be a strong suspicion that this would be genetic but no one knew exactly where to look. And, in fact, that’s still the case but what’s happened is that the cost has come down into the few thousand dollar range. For what  it used to cost to look at a single gene or few genes, we can now look at all 20,000 genes that code for protein, or for a little more money we can look at all of the DNA in a person’s genome. So that’s very exciting because it takes away a lot of the guesswork. We can look at the overwhelming majority of all of the genetic material of the person’s cells.

Jimmy:                    Now, that’s pretty amazing and considering only 10 years ago we (scientists) did that for the first time.

Dr. Angrist:            Exactly!

Jimmy:                    Dr. Gholson, you’ve been able to actually use that technology to identify genes in rare diseases. Can you tell us what you found and your experience with that?

Dr. Lyon:                Ah, yes. The  technology has taken a long time in coming. It was first developed by many people, some of them were at Cold Spring Harbor but many others involved in exon, they call it exon capture and sequencing. But about three years ago, after all that had been published, I started working in Utah. Because the families are quite large there and it’s really been historically a great place for genetics research, we started finding families to sequence. We did find one family with several boys – they died from the new disease. In that case, it was basically five boys over two generations with different mothers and we were able to use this new technology like exon capture and high throughput sequencing to quickly sequence the various exons. Then we used various software programs to filter and prioritize the variants and we were able to come up with one variant that at least in the context of the genetic background of that family and their environmental background. It appears that a mutation seemed to be very likely to be involved in causing that new disease.

Jimmy:                    That’s very exciting! Was it the first time anybody found such a variant for this disease?

Dr. Lyon:                Yes, it was. You know I think going back to even the time of Darwin, there’s been people who’ve always suspected that humans are all unique. I personally believe that every person on the planet is a unique genetic individual and that’s because there are 6 billion nucleotides in every cell of the body and it is estimated that you have 50-100 trillion cells in every human body and so with only 6 billion people on the planet, it seems as though everyone is likely going to be unique. But in the context of families where much of the genetic background is dissimilar, you can get these mutations , that are unique to the family and can lead to disease.

Jimmy:                    It is interesting. Dr. Angrist, you’re doing similar research. You are co-PI for Duke’s Task Force for Neonatal Genomics. It seems like this is sort of too good to be true. Can we be solving all genetic disease in this way?

Dr. Angrist:            No, it is too good to be true [laugh]. You know it’s a massive step forward, but of course with each new technology, each new advance, come new challenges. So, obviously if we’re now looking at 20,000 genes or 3 billion or 6 billion base pairs, instead of one gene or a few thousand base pairs, then we have many many many more times more data than we used to have. And so that becomes a challenge to store and to transport and mostly to interpret. We still do not have very many complete human genome sequences, so there’s still a fair amount of variation, this kind of – every one of us is like a snow-flake that Gholson alluded to. Every time we sequence the genome we still see things we’ve never seen before. We see spelling differences in the DNA alphabet that we’ve never seen before, and if we’ve never seen it before, we have no really good idea typically of what it means. So, that’s a major challenge particularly for one trying to help patients and trying to make diagnosis and trying to, as we say, correlate phenotype with genotype – in other words, trying to understand what genetic variants lead to which groups of symptoms. So that’s a major challenge.

Jimmy:                    These challenges…I think many of the listeners are interested because they have an illness and they think that they would like to be sequenced in order to figure out what’s going on, so who do you think, should ever get sequenced? Who should be the ones sequenced and when should patients consider, having access to this technology?

Dr. Angrist:            Well, it’s an excellent question and I don’t know that I am in a position to say that patient X should be sequenced and patient Y should not. I think we’re still sorting out grouping and figuring our way, figuring out which patients it makes the most sense to sequence. We’ve developed some criteria and some of them are purely logistical. So if we have a young patient with a group of symptoms that looks like a syndrome with a genetic cause, we’re more likely to go forward, and if we have access to the DNA from both parents- from both biological parents. From that we’re in a position to determine how any changes in the patient’s DNA we might be interested in. How they were inherited? Whether they were inherited from one or both parents, or whether they are a so-called new mutation that happened in the embryo and was not inherited from the parents.

Jimmy:                    Hmmm, so yeah it’s still a difficult thing to really be able to say which one person is a good candidate or not.

Dr. Angrist:            Yes. So generally patients with very severe conditions , if we have a patient who has symptoms that suggest an infectious disease, we’re probably not inclined to sequence their genome. If we have a patient with very minor learning disabilities we’re less likely to sequence their genome. So we’re looking for things that are severe, that are likely to be associated with profound changes in DNA that would jump out at us. And in a perfect world, we would like to sequence people for whom we might actually be able to use that information to better manage their care.

Jimmy:                    That’s great! So Dr. Lyon when you selected those early families, when you did sequencing, how did you decide to select them and why did you decide to work on those diseases?

Dr. Lyon:                It had to do with trying to be able to prove the causality, in terms of whether or not a particular mutation that you identify did – it’s about trying to prove that it’s really, is it necessary and sufficient to cause the illness. So, in this particular instance I met many dozens of families and as searching for a family with at least two affected children and at the end of it, as I said before, I ended up choosing a family that at that time had four affected boys where the grandmother had two of these boys and then each of her daughter had a boy so that it was a very obvious that the disease was passing down from the mothers and so it proved a lot easier to prove causality.

Currently there are many people who are doing exon and whole genome sequencing and they may choose a severely ill child. Even with the DNA from the mother and the father, you’re still getting potentially dozens of more variants in the child and you’re left not knowing for sure if that variant is both necessary and sufficient to cause the disease. One way to get around that is to find other people in the population that have the same disease and the same mutation and that is at least one other piece of evidence that is in favor of that variant potentially being involved in causing that new or different genetic disease.

Jimmy:                    At this time, I’m just going to ask you to remind the listeners that if you have questions, you want to post live, you can post any time. Our facebook page is www.facebook.com/raregenomics and there is a post there if you wanted to put in questions that we’d be able to answer live in five minutes.

So one interesting thing  Ghoslon, you’ve been writing about your experience of actually finding what’s potentially causative for a family and being able to communicate that and rectify that situation. Can you tell us a little bit more about that?

Dr. Lyon:                Ah, yes. I’m a doctor, I’m a psychiatrist and was trained in New York for a number of years and you know there are laws in place. CLIA which is the Clinical Laboratory Improvement Amendment Act is basically a law that was implemented that says any kind of testing that involves giving the results back to patients must be done in a clear, certified laboratory. And this law went to effect basically because there was a period in the 80’s when many people were doing testing of women and doing pap-smears and they weren’t doing it properly and they were getting all sorts of incorrect results. So this regulation went into effect and introduced standardization and a level of quality. So if you’re in a research lab and somebody sequences in your lab, on your bench, that’s not good enough. There are all sorts of quality regulation in place that say that any kind of genetic tests and other kind of testing has to be done in CLIA environment. So, I’ve been sort of going around, discussing the fact that it will be a good thing if we could get to a point where at least the initial germline, exomes and genomes for people – that they should be performed in sort of a CLIA environment.

This is then met with some enthusiasms and others are highly skeptical. That has to do mainly between this divide between researchers and the clinicians. Obviously researchers would like to just get on with sequencing thousands of humans and being able to do all sorts of research but clinicians on the other hand would like to give these results back to these people, and if you don’t do it in a CLIA environment, you’re left not being able to give the exomes or the genomes back to people. Instead, you’re left having just to go back to validate the mutation, a single mutation, in a CLIA certified laboratory and give back that single mutation to the person, but that you’re not able to give back all of the exome or whole genome to them.

Jimmy:                    Got it. Of course there’s the mechanism to return back the information it seems like.

Dr. Lyon:                Well, that’s correct. I sort of look forward to a society in which every person gets their majority of the whole genome sequenced and there are some sort of secure places, some sort of network, where each person can go back and look at their own genome and re-analyze it and update with new information. But in order for that to occur, the sequencing has to be done at least in a CLIA environment. Or with some sort of minimal quality standards otherwise it’s just not going to work for us.  To be giving back, haphazardly a bunch of exomes and genomes that were sequenced in a research setting where they’re asking for legitimate standards in place.

Jimmy:                    Yeah, that’s great. I think hopefully we’ll be able to communicate about that in the future. So Dr. Angrist, going forth, how does the future look like you think as this technology continues to drop in place and more people have more access to it, what would you see especially for patients who are listening and have questions about how this is going to impact my healthcare, or potentially have the disease that’s unknown. What does the future hold for patients?

Dr. Angrist:            Well, that’s a sixty-four thousand dollar question. I hope the future looks the way that Gholson described it, where people have unfettered access to the information if they wanted. I think we’re still ways away from that unfortunately, given the pushback I get when I try to make this case to physicians and even my colleagues on the institutional review board at Duke, that reviews research. There is still great reticence and there is still a lot of fear that the public is not ready for their own genomic information and won’t understand it and it’s meaningless anyway, so why should we bother. I think events and technology will ultimately win the day and those objections will simply not be tenable. It’s simply too difficult to keep this information under lock and key because it’s too cheap and easy to get it and it’s getting more so over the time.

Jimmy:                    Thank you! A little break here from Rare Genomics Institute. Both Dr. Angrist and Dr. Lyon actually are partners with us and we’ll try to help patients with rare disease that don’t have a diagnosis, that don’t have research studies and to be able to create these sequencing projects and I think like it was mentioned, we don’t take all comers. But if patients are good candidates for sequencing, we have investigators who like to partner with families to hopefully be able to find what’s causative or to push forth research a little bit and that’s sort of our hope here at the Rare Institute of Genomics. Thank you so much Dr. Angrist and Dr. Lyon for your expertise.

Dr. Angrist:            Well thanks for having us!

Dr. Lyon:              Thank you!

Jimmy:                    In our next half hour, we will be discussing specifically about one disease which is ataxia. We’re really lucky to be able to have one of the experts here, Dr. Perlman. Thank you Dr. Perlman for joining our show.

Dr. Perlman:         Thank you for inviting me.

Jimmy:                    Thank you! Dr. Perlman is the Director of the Clinical Neurogenetics Program and the Ataxia Clinic at UCLA since 1986 and has a variety of clinical interests in inherited ataxias. When she did her fellowship, she did research in the biochemistry of Friedreichs Ataxia, before we even knew what genetic cause was. She is a member of the Collaborative Clinical Research Network for Friedreichs Ataxia, the Cooperative Ataxia Network, as well as the Huntington Study Group, and also is in national organizations that are engaged in furthering clinical research for the treatment of neurogenetic disorders. She has received numerous awards, and when I was actually able to meet some people in the Ataxia community recently, when they heard that Dr. Perlman was going to be on the show, they were ecstatic and she is really highly recommended and we’re really privileged to have you.

Dr. Perlman:         Thank you.

Jimmy:                    So Dr. Perlman, ataxia seems to be a really broad topic. Can you tell us what is ataxia for those who don’t know?

Dr. Perlman:         Ataxia is technically classified as problems with balance and coordination that relate to the cerebellum which is the part of the brain that controls balance and coordination. Ataxia can also be caused by changes in connections to the cerebellum which would include the connections from other parts of the brain and also the spinal cord. The inner ear connects to the cerebellum so somebody could have inner ear problems with symptoms that look very much like and would be called ataxia. They could have changes in sensitivity, for instance, in their feet or legs which would decrease information going to the cerebellum and could cause problems with balance.  Problems with walking that could be called ataxia because of lack of that input. So the key player as it were in the diagnosis of ataxia is a problem with the cerebellum either in the cerebellum itself or in other pathways that are connected to the cerebellum and provided information. There are walking and balance problems that might initially be called ataxia but turn out into something else. Changes in muscle tone or strength can alter the way a person walks. If somebody has severe tremors or twitches, it may alter balance and coordination. If someone has a problem with vision and they can’t see well, they may be clumsy because of a vision problem and the cerebellum could be just fine. So, when somebody has been presented with a diagnosis of ataxia or they think they have ataxia they should make absolutely sure that it’s not something else that looks like ataxia and should be evaluated in the clinic in a different way.

Jimmy:                    Got it. Well, so there seems to be a lot of things that can be warned to cause ataxia and lot of things that sort of mimic it. So, what’s a normal cause and what do we recommend for them when they think that they do have ataxia?

Dr. Perlman:         If someone thinks they have ataxia, the first thing they should do is to be examined by a neurologist, either an adult neurologist for an adult or a child neurologist if there is a child to make sure that those symptoms of changes in balance and coordination and changes in speech are coming from the cerebellum and exactly can be truly called ataxia. The physician would then take the person through an initial work-up that would include testing to rule out common causes of problems in the cerebellum. Things like brain tumor, things like stroke, and multiple sclerosis are commonly known to affect the balance center and are easily ruled out by brain imaging or other testing.

It’s possible that those initial tests, brain imaging, initial blood work to look for vitamin deficiencies or poisons or toxins may not be informative. The cerebellum may look pretty good even though it isn’t behaving properly, vitamin levels could be fine, the rest of the body’s metabolism could be fine, there could be no sign of poisons or toxins. Then they would go into the second round of testing which typically is going to include testing the immune system. In the last 10 years, I think we’ve appreciated that problems in the immune system, bad antibodies as it were, can selectively attack cerebellum and cause ataxia. And there are many causes of that. So it should be looked for because many of them are treatable.

The other area is genetic. If there is an obvious family history, then genetic causes of ataxia come to mind immediately. But if there is no family history (there might be no family history for a number of reasons, the person could be adopted, prior history could be hidden, it could be the type of genetic disease that shows up in one generation but may not show up in the next – it may appear to skip generations)but at its heart, it’s really a genetic problem, or it could be a recessive genetic problem where the person will have to have two doses of the pair of gene to show symptoms. All carriers with one dose of the gene would not have symptoms. So there could be no prior family history. So when we’re choosing individuals in our clinic that we might want to push on into a more intense genetic work-up which might include exon sequencing, usually we look for family history. But we won’t let that hold us back – you know anybody who has a condition that could be genetic, slowly progressive, fairly symmetrical in the adult population especially, we would consider some the least limited type of genetic testing and obviously are quite thorough with the non-genetic factors. Even in our population, we’ve seen almost 3000 individuals over 10-15 years with various types of ataxia. For about 40% of them, we have been able to assure the families that it is genetic and majority of the families have actually been able to find a genetic cause. The other 60%, common genetic screening was negative and looking at the immune system was not productive; all the other work that was done by us and the outside physicians was not informative. But there is still a possibility that there could be a rare genetic factor, a genetic risk factor that sensitizes them to something in the environment that the rest of us are not sensitive to. We’ve continued our clinical research in our adult patients for sure, looking for any genetic factor, an obvious one or genetic risk factor that might be part of the picture. We still, however, are not successful about 50% of the time in finding any cause for the ataxia, genetic or non-genetic, and we try to continue working with these people.

Jimmy:                    Prior to this, we mentioned sequencing, or genome sequencing as we’ve been talking about that in the first half. So, how do you see genome sequencing changing genetic testing for ataxias?

Dr. Perlman:         I think as our initial speakers said, it is a much cheaper way to cover a broader number of genetic mutations. Currently there is a popular gene testing panel, which if you order every test on there, (which is probably not advisable because some of them are quite rare, some of them are different)… I certainly wouldn’t recommend trying to get the insurance company to authorize $17,000 to get to that entire panel.

Jimmy:                    Wow!

Dr. Perlman:         However, for less than half of that you can have exon sequencing done that will show you many of the genes that are on that other panel. And many other genes besides that may not yet be not known to be involved in ataxia conditions. And that’s where the research comes in to determine these changes in the pattern in a specific gene that may come out of exon sequencing – is it known to be associated with some interaction in the cerebellum that may cause ataxia? Has it ever been reported by anybody else in the literature? Have those reports stood up to research or have they been knocked down? This sometimes happens – you find a change in the gene and get all excited and further testing will show that it’s not actually involved in causing disease at all – but that original paper is out there continuing to confuse people in the literature.  So, I think the use of exon sequencing to look for changes in genetic patterns that might signal the gene involved in causing ataxia, or the risk gene that might be involved in changing the cerebellum. It will have to be interpreted by people who are experts.

In my institution, we have begun to do CLIA approved exon sequencing and we work with insurance companies to get it paid for. And we work with the Committee of Genetic Experts at my institution who will go over all of these results before we try to explain any of them to the patient to make sure that we are not giving any information that ultimately would be proven false. We don’t want to lead any people in the wrong direction.

Through commercial testing from other companies with the available single gene test, we’ll find a little change in the gene, they’ll post the result as unknown significance and people get kind of excited, ‘oh, that’s the kind of ataxia I have!’ and in reality, it’s not. So I’m hoping that from sequencing we can strengthen our ability to find ataxia genes and then figure out what they do so that we can design better treatments.

Jimmy:                    Yeah!

Dr. Perlman:         I think you’re going to appreciate that the time to a diagnosis can take months and sometimes years.

Jimmy:                    For a normal patient, how long does it take?

Dr. Perlman:         I’m getting brain imaging, I’m getting blood work… within a month. We can get all the first line stuff done. You can get a lot of the testing of the immune system done. So within 4-6 weeks, you should have enough information to say whether it’s not one of the common causes one of the common non-genetic causes. The available genetic testing–if you have a strong suspicion that this person has for instance Friedreich’s ataxia. It looks like Friedreich’s – you’ve seen other patients with those diagnosis, you know other people with that diagnosis. You can send a single gene test for Friedreich’s and get a report back again in about a month. If, however, you’re going to invest in exon sequencing, depending on the lab you’re working with and certainly at my institution, because of the additional quality control and genetic consultation that is involved, it can take up to three months to get that report back. And if you’re one of my patients that I’ve been following, I have some patients that I’ve been following for 30 years with progressive forms of ataxia, we start on having a diagnosis for them. Some people we banked DNA on, that was before gene testing was available. Gene testing came out; we started looking at their DNA in the research labs. Ten years later, we figured out, ‘oh, that’s what you have!’ and, so we try to maintain contact with people that we have seen for treatment or consultation so we can continue to update them.

I think one of the best ways that people can stay in the loop in their own physicians or research physicians is to be a part of an ataxia registry where they are registered and there are several ataxia registries out there through the National Ataxia Foundation, through the Rare Disease Network, where people can put in contact information and the type of ataxia they think they have, so that they can receive information about research going on in their area.

We suspect in the United States that the incidence of ataxia, genetic ataxia is probably about 5 in a 100,000. Which means that if we look at the population of 330 million, there could be around 15-16000 people with various types of genetic ataxia and an equal number, if not more, with non-genetic ataxia. I know that registries that I am aware of have at most 600-700 individuals in them. There are a lot of people that haven’t stood up to be counted, have not put themselves in a registry where they could be a part of the numbers that will drive for the research. You know, when the funding agencies see that we have 5000 people with all types of ataxia in registries available for clinical trials for instance or other research, much more likely to give more money to a researcher because you know you can find people to do research on. So it’s really important for people to be registered.

Jimmy:                    Wow! This thing has so much going on. The registry would be important especially in finding out information for the trials and increasing research.

We’ve got a bunch of questions submitted by patients specificallywith cerebellar ataxia. One of the questions is, are there things that we can do to sort of slow the progression or are there specific diets and nutrition that you would recommend for someone with ataxia?

Dr. Perlman:         Absolutely. Some things that have come out through clinical research in people with ataxia and in animal studies of animals with ataxia is that exercise absolutely can help improve symptoms of ataxia and even stabilize people for a longer period of time, potentially slowing progression or enabling them to keep up with an underlying progression.

The types of exercises that are found to be helpful – rhythmic repetitive exercise that keeps the rhythm going – feeds back information to the cerebellum like practicing the piano, the more you practice, the better you get. So practicing walking, practicing rhythmic repetitive exercise on a daily basis will improve performance.

Strengthening core muscles will improve balance. If somebody has tightness in joints or tightness in muscles because they can’t use them while stretching, it will improve mobility which will then itself improve balance and coordination. So we usually recommend that everybody work with a physical therapist to develop a daily exercise program that includes something rhythmic and repetitive, cardio for instance, meets that. Something that works on the core muscles and then stretching if appropriate.

There are symptomatic medications that can stimulate the nerves in the cerebellum to work better and if you typed into a medical search engine ‘ataxia and treatment’ you would find hundreds of articles about various available medications that have been used to treat the symptoms of ataxia.

Amantadine, which is an anti-flu agent, Buspirone, which is an anti-anxiety agent – there was recently a publication about Varenicline or Chantix which is a stop smoking agent and another publication about Riluzole, which was approved for use for people with Lou Gehrig’s disease.  In the European study, it appeared to help people with symptoms of imbalance and incoordination. And these are just of first four of many that seem to have some benefit for symptoms. None of them are disease-modifying. If you have a progressive form of ataxia, they won’t stop the progression, they won’t cure the ataxia, but they seem to be able to get the cerebellum to work better despite the limitations that it has.

Vitamins, nutritional supplements… there is a load out there. There is a lot of research focused on the road of anti-oxidant vitamins and anti-oxidant supplements in treating a variety of degenerative brain diseases including ataxia, including aging for that matter. So, if an individual wanted to pick one or two reasonably safe antioxidants and try them for six months to see how they feel, to see how they do – very appropriate.

But they should be wary shoppers. They should not invest a lot of money in an interesting brand that have a lot of testimonials behind it suggesting it can cure ataxia because most likely it will not do that. But sticking with the simple ones like Co-enzyme Q10, resveratrol, Vitamin E, there are a number of antioxidants that have been in clinical trial in a variety of brain and medical diseases which do seem to have an impact and are worth a trial.

Jimmy:                    Hmm. That’s very interesting. Can you tell us a little bit about clinical trials of ataxia? One of our listeners wrote in, ‘I was wondering why there are not more clinical trials? Suppose we have difficulty in getting the clinical trial… in that individual, how do they identify their ataxia?

Can you comment a little bit about the current clinical trials that are existing for ataxia.

Dr.Perlman:          Clinical trials. There are two type of clinical trials. One would be a drug for symptoms and there is currently a study going on in Florida with a drug that may have symptomatic benefits for ataxia, may or may not modify the course of the disease. So, as ideas come up for available drugs or new drugs that may improve the symptoms of ataxia. The individual, the physician researcher who wants to sponsor that trial has to get funding but for an available drug, he may not be able to get the drug company which has no interest in pouring money into a new use for an old drug if they’re not going to get a lot of money back from it. If it’s a research drug that has not been tried, but seems to have the potential for relieving symptoms, then again they would have to get funding, they would have to convince the FDA that it’s safe and effective to use, and for any new drug, whether it’s a symptomatic drug or a disease modifying drug, if it’s a brand new drug, the first light goes off in somebody’s mind. It can be 15 years and millions of dollars to bring a drug to a point where you can say this drug seems to be helpful and this drug does not seem to be helpful.

Certainly for gene therapies, depends on having a very specific form of ataxia with a genetic factor that has been identified and then that very very rare group of drugs under development that can actually modify the genetic changes that are going on. There are indeed many drugs of that type in the pipeline but very few have reached the point in animal studies and safety studies to where the FDA is willing to let them move forward in the human trials. So, the good ideas are there, but the pipeline is very expensive. It’s a number of trials that actually make it through for people to be in are very small. And once the trial is posted, there are going to be restrictions. They may want to study the drug only in people with a certain type of ataxia or people in a certain age group or a certain level of disability recognizing that if they want to study to have statistically significant results, they have to control as many variables as possible.

If it’s more likely that younger people will respond and older people will not, then we restrict the study to younger people to try to assure that we get the best data with the best statistics that will make the best case to the FDA to approve that drug. Maybe after the drug is released, it will be used by everybody, but actually get into a clinical trial, you know you have to get that clinical trial that have been running and then you have to meet those criteria that the people going through the clinical trial is going to give them the best data. So it is frustrating. It does seem to go through very slowly. We have a dozen new drugs for arthritis, but having just one drug in the clinical trial for ataxia in a year is a huge achievement and we have a lot of devoted clinician researchers in basic scientists out there trying to get this done. We are in much better shape than we were in ten years ago.

Jimmy:                    What does gene therapy look like for ataxia? Is that something that is in the near future for the patients, or is still sort of more sort of theory vs. practice?

Dr. Perlman:         You know, it’s interesting… In some disorders with known gene and a known mutation, for instance, Friedreich’s ataxia, in which one gene has a very specific type of mutation and in 95% of people we have it, there have been drugs developed that can make that gene behave like a normal gene.

Of the several different classes of drugs that are under development, one has gone into a phase 1 human trial, not in the United States but outside the US. So, after 10-15 years of intensive research, the first, as it were, gene therapy for Friedreich’s ataxia is entering human trials. For some other ataxias, let’s say, dominantly inherited ataxias which are numbered Ataxia Type 1, Ataxia Type 2, Ataxia Type 3. Again, there seem to be one or two classes of drugs that seem to modify the effects of gene mutation and prevent the bad gene from causing damage. One of them is entering the phase 1 study. One is just at the threshold of the FDA, hopefully giving it the go-ahead to go in to human trials. So I think it’s been only 15 years since the first genes for ataxia were really nailed down. So, I guess we’re at that point – at 15 year mark, where some of these very carefully developed gene therapies as it were finally getting into the human trials. And there will be more. But the key thing is safety, you know, you start manipulating the human genome and a lot of things could change.

A drug you think is targeting your gene of choice might be accidentally targeting other genes that you don’t want to manipulate.

Jimmy:                    Yeah. It’s been an exciting time and hopefully with these we’ll be able to help more people. We have some questions that listeners have submitted live. One of them is about the caretaker of a person with ataxia. Do you have advice for caregivers and others helping them on how to be supportive of people they are caring for?

Dr. Perlman:         The caregiver, whether it’s a caregiver, a significant other, or a family member, has to recognize that from the medical point of view, safety is our number one concern. We would want to with the ataxia patients’ permission be able to include the caregiver in medical discussions about proper treatment, proper exercise, are there any drugs or vitamins that might be helpful and also safety in the home. Ataxia, in general, does not kill people, but falls and injuries will. Immobility, not moving around, can predispose to infection, and infection can cause sepsis which can kill a person. Not taking care with eating – eating too fast, eating the wrong kinds of foods, swallowing down the wind-pipe, choking – can be a life-threatening emergency. So our number one concern for improving the length of life in anybody with ataxia is preventing falls, preventing choking, maintaining good general health and maintaining mobility at whatever level a person can do.

It is extremely important to maintain independence, I think, for any of our mental health. We want to think we’re independent, we want to think we have some say in what we’re doing and I think a caregiver needs to respect that. I think the caregiver, certainly if the person with ataxia has severe disability and that caregiver is providing a large amount of care, the caregiver him or herself has to have time-out. They need time to themselves. They need to be rested. They need to protect their own health and mental health when they’re taking on this such an important role being a caregiver for someone. It’s important to never to give up for the caregiver or the patient. They need to seek information, what’s new, what’s going on? They can run around the country seeing experts or they can network with other people with ataxia and I think, certainly in my experience ataxia people have learnt enormous amounts from each other and I’ve learned an enormous amount from my patients.

Jimmy:                    Great! So if there are patients who want to learn more about ataxia, besides getting support in the form Ben’s Friends, are there resources that you would recommend them to look up online to learn more about ataxia?

Dr. Perlman:         There are very good sources. One is the National Ataxia Foundation and their website is www.ataxia.org. They have a variety of educational materials, they have postings about current research, they will answer questions, they will find experts to answer questions if there’s a question that they can’t deal with. I think for anybody with any form of ataxia, it is a wonderful initial resource and the website has links to other websites as well.

For people with Friedreich’s ataxia, there is another website that is www.curefa.org which has more specific information about current research, current clinical trials, what’s known about ataxia, and links to other sites specific for a person with Friedreich’s ataxia and both of those websites have links to registries – the registry for Friedreich’s ataxia, the registry for general ataxia, so that people can kind of do one-stop shopping at either of the two websites.

Jimmy:                    Great! Thank you so much. The hour is up, but Dr. Perlman has actually agreed to stay a little bit longer which will be a bonus section – separate from the podcast. So as a part of this podcast, we’d like to formally say ‘thank you’ for your time Dr. Perlman.

Dr. Perlman:         Thank you for inviting me. I think you can see that I take any opportunity I can to educate people, to help them find resources. Patients at my clinic have heard this lecture many times. So I think it’s important for everybody to get this information and to be advocates–to share it with other people.

Jimmy:                    Well, thank you. We definitely appreciate it, having known of your many efforts for this community, and a lot of the other patients appreciate this also. Thank you very much!

Dr. Perlman:         Thank you.

Jimmy:                    So that concludes our hour. Some people have remarked online asking about the next topics. We’re actually working with Ben’s Friends to go through the different disease communities and Ben’s Friends will be surveying and assessing interest on different diseases. In the future we will be covering other future technologies in the first half and other diseases in the second half. Our goal is to really provide the resources for patients on the most cutting-edge of science as a resource for rare disease as well as the one specific disease.

Thanks for everybody for tuning in.

Thanks to Jim Golden for writing the column!

View the article here.

Check out the story here!

Today, RGI and Assay Depot are announcing our joint Rare Disease Research Competition, Be HEARD (Helping Empower and Accelerate Research Discoveries). This is a great opportunity for rare disease groups, or single families, to team up with researchers and get some life-saving research done on their disease!

Submit project proposals, and potentially win $10,000 cash and over $400,000 worth of research services to forward the study of rare diseases!

For more information, check out our press release or the challenge website!

And, some bonus material from Dr. Perlman answering more questions about ataxia!

Listen and educate! In the words of Dr. Perlman, everyone can and should be an ambassador for ataxia.

Thanks again to everyone that attended, and especially to our amazing experts, Dr. Lyon, Dr. Angrist, and Dr. Perlman!

In the future, if you would like to follow our rare disease podcast feed, do it here.

If you have a suggestion for next time, or want to give us feedback, fill out this form!

We had a great time with Drs Lyon, Angrist, and Perlman talking about rare disease research and ataxia! Hopefully you were able to join us, if not, the recording will be posted soon.

If you did join us, please fill out this form to give us some feedback, and if you want to suggest a topic for the next podcast!

If you have ataxia or are interested in ataxia, RSVP here to this amazing opportunity with some very important experts- Dr. Lyon Gholson, Dr. Susan Perlman, and Dr. Misha Angrist! You don’t want to miss it!

The Shad Valley interns completed their intensive three week program with us, and did some amazing work! Congratulations to all of them, and we appreciate their hard work so much!

We have a podcast series coming up planned with Ben’s Friends! Await more details as we get into the planning process!

As an update on the articles about Maya (and us), these following places have written about the story:

Crowdkickoff, Singularity Hub, Bloomberg Businessweek, SF Gate, St. Louis Business Journal, Bmore media, Startup Leadership Program, Faith and Leadership, CauseVox, CrowdStation

With the assistance of such great articles, we’re hoping that we can help spread the word to more we can help!

Also, Caregiving Cafe, a resource site for caregivers of their loved ones, was kind enough to post about us on their blog- check it out!

Our SWAN/RGI Transcript is finally ready (see below)! As mentioned before, the unanswered questions will still be answered- they are in the works!

Thanks again to everyone who attended, and if you didn’t, yet would like to give us feedback, please fill out this form.

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AMY : Welcome, everyone.  I’m Amy Clugston from Syndromes Without A Name USA, or SWAN USA for short.  Thank you for joining us on our first conference call of “Ask The Expert.”  Thanks to the Rare Genomics Institute team for their work on bringing this opportunity to our community.  A quick disclaimer for you all today on this conference call: we will be sharing a lot of information — this information should be used for educational purposes and should not be considered a replacement for consultation with a healthcare provider.  So contact your healthcare provider if you have questions about your health.  Let’s welcome our panelists.

Jimmy Lin.  He is the president of RGI and he founded the Rare Genomics Institute. He received his MD and PhD from John Hopkins School of Medicine and is an expert in next-generation sequencing and cancer genomics.  He is a 2012 TED fellow.

Marisa Dolled-Filhart.  She is Vice President of Strategic Alliance and Partnership for RGI.  She received her PhD from Yale University in Genetics.  She has several years of operational and strategy experience from scientific and business development positions at HistoRx and Quintiles, focused on personalized medicine.

Naira Rezende is the Vice President of Patient Advocacy and Polices for RGI.  She is a PhD candidate in Molecular Biology at Cornell University.  She has been a research fellow at many prestigious research institutions, such as Yale and MIT.

Would either of you like to share anything about yourself today?

JIMMY : No.  Thanks for inviting us!

AMY : OK.  So I’m going to start by asking pre-submitted questions that some of you might have shared with us previously to this conference call.  That will be for the first 45 minutes.  During that time, you’re welcome to post questions on RGI’s Facebook page at facebook.com/raregenomics.  You can comment on the post that is currently being posted.  And you could send a message if you would like it to feel a little more private.  We will then spend 15 minutes answering those questions that were posted.  If the questions are too specific, we will try to answer them in a general way.  And RGI will answer them individually as well.  All questions that haven’t been answered on the call today will be answered and posted on RGI’s website.  So let’s get started with those questions.  We will start with, “How many people in the world have rare diseases currently diagnosed?”  Jimmy, would you like to take that one?

JIMMY : Yes.  Thanks, Amy.  Again, I just want to say thank you for inviting us — this opportunity to partner together and hopefully we’ll be able to answer some of the pressing questions that the patients have.  So, yes… the first question…  ”How many people in the world have rare diseases? Are rare diseases really rare?”  And that’s a great question.  Rare diseases are rare in themselves.  There are over 7,000 rare diseases and in the U.S., it’s sort of a legal definition.  If less than 200,000 people have it, then it’s considered a rare disease.  And most specifically for them having special status when they’re developing drugs.  However, the 7,000 diseases when added up together affect tens of millions.  In fact, it’s almost — in the U.S: 1 in 10 people have rare diseases.  So in the world, the global number is about 350 million people with rare diseases.  So although individually rare, rare diseases together are actually very common.

AMY : OK.  Thank you, Jimmy.  ”What kind of current medical technology is the most useful for rare genetic disease research?”

MARISA : There are a variety of methods that can be used for rare disease genetic research and in particular for diagnosing rare diseases.  One of the most common method traditionally used is the family pedigree.  So tracking the different relatives within a family, understanding who is affected by a disease and who is not- tracking of symptoms.  Those are some of the basic components of rare disease diagnosis.  However, there are a variety of medical technologies that can be used to help further study and identify and diagnose rare diseases.  One of them is called karyotyping where the chromosomes of the person is looked at to see if there are any major chromosome changes or rearrangements that are different than what might be expected.  And that is useful for identifying some large chromosome changes, but can miss some of the smaller changes.  So there are some other methods that can be used as well which can give a bit higher-resolution look at chromosomes for rare diseases.  And one of those is called Array-CGH, where CGH stands for comparative genomic hybridization.  And that can look at chromosomes at a higher resolution, but not at the gene level.  So some of what we’ll be focusing on discussing today are some of the latest advancements and technologies related to sequencing.  We’re looking at the DNA at a base-pair, letter-by-letter method in order to look to see if there are any changes in the DNA or mutation that would be responsible for causing rare disease.

AMY : Thank you, Marisa.  On to the next question, “Have there been any new advances in the past two years with the microarray testing?”

JIMMY : Yes.  It’s a good question.  Another question too is, “What kind of advances in general have been in genetics these days?”  Like Marisa mentioned, the family pedigree is going to be very, very important, and that hasn’t changed.  So that is more predictive than anything else.  To karyotype some things on the chromosome level, when it’s large, hasn’t — it’s a broader, larger look.  The things that are of higher density is microarray.  What microarray does — it looks often at specific locations.  And they have these chips that look at positions in the genome.  And what has advanced is that more and more number of positions are now examined.  It started out within a hundred of thousands, then half a million, now people can do over a million.  So it is now higher density and allows for a deeper look and ultimately, I think, eventually we’ll be able to look at every single base pair using whole genome sequencing.

AMY : OK.  To add on to that, “What has been available now that wasn’t in 1989? So what is the future progression for looking at signs and symptoms between what some other family members might be passing on?”

JIMMY : Yes.  So there was specific that year of 1989 that the person who submitted the question asked for.  And it’s interesting because it is humongous how much has happened since the year 2000, so 1989 is a while back.  The human genome was sequenced about 10 years ago, around 2001.  And since then, there has been a dramatic increase in the ability to sequence.  Ten years ago, we sequenced the first human for $3 billion and now we can sequence for about $3,000.  So sequencing is actually now a possibility for patients and there have been many, many advances since 1989, of which sequencing is one of them.  I don’t think there was even microarray.  Yes, there was no microarray in 1989.  There was some simpler sort of chromosomal studies and karyotyping, but most of these technologies we are mentioning did not exist in 1989.

AMY : OK.  Thank you, Jimmy.  ”What are families to do after ruling out several syndromes and with two negative microarrays?  Is it worth it for families to pursue continued genetic testing?  Or have possibilities been exhausted at that point?”

NAIRA : Not yet.  It is important for a family to continue pursuing this testing,  and sequencing technologies are the way to identify a new patient-specific gene on a single base pair and to come up up as a diagnosis.  One of the things that I want to explain on this answer is that microarrays and genome sequencing are fundamentally different.  Both of them look at the genome and look at many, many genes at the same time.  So both of them are more than just a single test  looking at one mutation in one gene.  But the way that they’re structured differs fundamentally.  So in a microarray, you take a look at the genome and you hybridize it to a number of pre-established sequences.  Even though it’s a global approach, there are a number of sequences that you are looking for, and you’re looking for a difference in expression between, let’s say, the mother’s genome and the child’s genome.  What you get with sequencing technologies is that you get a specific base pair difference between the genome of the mother and the child.  And that can give much more of an answer in diagnosis.

AMY : OK.  To add on to that a bit, there are different devices for sequencing, and we’d like to know, “Which is better?  What kind of sequencing methods are better and why? “

NAIRA : There are many different companies that make devices for sequencing.  And most of the focus of sequencing right now really is in the analysis.  When you’re doing the sequencing, what you’re going to get is the base pairs in their genomes, and what the scientists really are looking for are mutations when they compare the child’s genome with the genome of the parents, what really stands out are the differences.  Illumina is one of the companies that makes such sequencing devices, Life Technologies is another.  There is no definition right now in which one is better, and why each one is better.  Sequencing is the most sophisticated approach that is out right now, and what you’re really focusing on now is the analysis of the data, which is one of the things that RGI has developed its scientific partnerships for. That way (with the scientific parnerships) the quality of the analysis of the data can be the highest possible, that means we can identify a mutation. The focus should not exactly be in which of the machines or the company that is used to be the sequencing.

AMY : OK.  Thank you.  So families — if they have already explored all these methods — what are their other options? They’ve seen many doctors, what else could they possibly do?

NAIRA : Genome sequencing right now has about a 30% success rate in identifying the causes of the disorder.  This is actually higher than anything else that you can have with most of those undiagnosed diseases.  That’s actually why — specifically why they should pursue genome sequencing because in many cases other methods have failed. I lead the advocacy team at RGI, and we speak to a lot of those families.  It’s very common that a mother describes to me that they have been to five or six different clinical geneticists, have tried every single test they possibly can, and they still don’t have a diagnosis.  They know that there’s a strong genetic component to it (the syndrome) because five or six clinical geneticists have evaluated (the child) and come to that conclusion, but they still don’t know what could be behind that.  So that’s a perfect family that’s a perfect candidate for genome sequencing.  And you do have now this 30% success rate in identifying the underlying causes of these disorders.

JIMMY : Yes.  And then what’s amazing is that in the past, I think microarray and other methods are a great.  Like karyotyping.  I mean there’s things that they can find if there’s a larger change.  Microarray can find large deletions, and what we’re specifically talking about are patients that have gone through traditional testing and have not found what has caused it.  And that — of those, people have been able to use genome sequencing.   And there’s some great programs that already do it.  For example,  the NIH has the UDP Program, which I believe — Amy, your family has been through — there’s also — University of Washington, there’s the Mendelian Centers, there are great places doing in it.  And we at Rare Genomics are helping those who potentially are unable to connect to those places, or we provide some connections to those places.  There are a lot of different possibilities, of which genome sequencing is one of the most powerful.

AMY : Thank you.  OK.  ”What is the difference between exome and whole genome sequencing?”

MARISA : That’s a great question, and I think a fairly common question.  So the two main types of sequencing as you mentioned are exome and whole genome sequencing.  What exome means is that there’s a portion of the genome that’s called the coding portion, that essentially scientists know is creating the genes that are used to create proteins, that are the functional aspects  of our genome.  And that represents about 1-2% of the genome.   And historically, about 85% of diagnosed genetic diseases have involved mutations in this specific area called the coding area of the exome, within the genome.  So essentially they’re short functional DNA sequences.  And by focusing on just exomes and exome sequencing, it’s more efficient and more effective currently than whole genome sequencing, because you can imagine that with millions of base pairs of DNA, there’s a lot of information from a bioinformatic approach in order to identify the specific changes between parents and children that are occurring.  They’re actually causing diseases compared to naturally-occurring variants in the DNA sequence.  So one thing to know about exome sequencing, as I mentioned, it’s about 1-2% of the genome.  There are some limitations to exome sequencing.  So if for example there’s a disease that’s caused by changes in the structure or if there are mutations outside of the coding region, those are areas that wouldn’t be analyzed through exome sequencing.  So that’s something to be aware of.  However, the areas served outside of the exome, the function and the utility of those areas are not as well-known and we hope that there will be additional advances in our understanding of those areas through whole genome sequencing that can hopefully identify diseases that are not diagnosed through other traditional methods we’ve mentioned or through the use of whole exome sequencing.  Whole genome sequencing, as I mentioned, looks at all those genes that we know have functions as well as less-studied portion.  And hopefully in the future, the cost of whole genome sequencing will continue to go down and hopefully the informatics approaches that currently are more challenging with whole genome sequencing will be resolved so that that could be something that is used more routinely, the way that exome sequencing is starting to be used for diagnosing rare diseases.

JIMMY : So I think a good way to think about it, I just came off a plane.  So I sort of have this image in my head of — I’m flying over the Midwest and most of it is prairie lands and there’s certainly a — I mean, once in a while, we’re flying over sort of cities.  Interestingly, your genome is mostly stuff that we actually don’t know and they’re actually not expressed.  These are sort of mostly space.  And then the genes that we’re talking about — actually comprise of only a very small part and which Marisa has talked about sort of between 1-2%.  And within the genes, there’s specific parts of the genes that are expressed called exons.  And those are the parts that potentially are the things — the parts that we understand most.  So what scientists are doing now is, first, focusing on those areas where we think there’s a high concentration of function and only a very small proportion of the genome.  But those are the areas you understand most.  And then later, as technologies get better, when we can look at the whole thing, so while sequencing is still not super cheap, we’ll emphasized on the most important part which is the exomes.  And all the exons together is called the exome.

MARISA : One other thing to mention — I’m thinking about Jimmy’s analogy to looking at the U.S. from a plane — is that you can think about some of the different methods we’ve been talking about for genetic analysis and for use in diagnosing rare diseases in that same type of context.  So if you’re flying in a plane and you’re looking down a city in the U.S., you can see that as — if you’re looking for a red car on the street — you’re using karyotyping. It will let you know if there’s a lot of red cars, or if there are blue cars instead of red cars, or see something sort of major — something that you can really view from high up above, and that is kind of what karyotyping does, is let you understand sort of some major changes or show if there’s a big large crowd of red cars, you would see it.  At the next level of some of these microarray technologies, where it’s not so much about looking from the plane instead of just seeing sort of large expanse of country.  You can kind of zoom in on a part of the city.  So higher resolution.  You might be able to see that there are sort of a lot of large buildings, or if you’re flying at night time, you see a huge cluster of lights but you may not be able to see things individually.  And so then if you zoom in further, you can see sequencing as being able to see a single red car driving on the street.  And that kind of gives you the different levels of resolution that are possible with genetic analysis.  And so as technology has advanced, it allows us to zoom in closer and closer, where they may be some disorders in which a low-resolution, or just looking outside of the plane window is sufficient to identify a major change that’s causing disease.  Or in some cases, for other rare diseases you really have to zoom in to that sort of individual car from a plane level in order to be able to identify a change that is causing a disease.

AMY : OK.  Thank you very much.  Great description. So, “How does this work?  Why do we need to sequence parents?”

JIMMY : Yes.  Often, when we do sequencing, we don’t just sequence the child, because on average, everybody’s genome has a lot of changes.  And what is a a good way of sort of subtracting those changes is a child gets half of their genome from mom, half their genome from dad.  And they can compare if that gene comes from mom or comes from dad, and mom and dad are OK,  that sort of change probably — if it’s also a mom and dad is probably not what caused the disease, if it’s a very — what’s called the penetrative, if that’s the change has causes a big deal. If it causes a big deal but it’s also in mom and dad, and mom and dad are healthy, then that way they could subtract.  So genome sequencing is very good because you can — there’s a lot of changes, right?  If you imagine two maps, we’re talking about from the plane, there’s often a lot of changes in every person, so then important thing is from all those changes that exist, the whole genome holds tens of thousands, which of them actually are important and which of them cause disease.  So what we do is we sequence mom and dad.  Take a one out of mom and dad.  Then we compare them with the general population, and see whether they exist in the general population, if they exist in high frequency, they’re probably not a disease.  And then from the ones that are left we then look at, “You know what?  Which ones are the ones that are broken? And do we know that the gene that’s broken does something specific that’s related to the disease?”  And from that process, we can sort of then shorten the list to sort out top candidates that we think are potentially causative of a child’s disease.

MARISA : Jimmy makes a good point about some of the different changes that occur.  Some of them maybe sort of more naturally occurring variants that may exist in the general population. But you also mentioned thinking about genes that are “broken.”  So what that means is that sometimes when there’s a change in the DNA sequence, ultimately the DNA sequence is used to create proteins and so you can think about it in the sense that in some cases there may be a change that doesn’t ultimately have an effect.  So can be almost sort of like an ineffective… or a change that doesn’t actually impact the resulting proteins.  However, there are some changes that could then end up causing the proteins to be shorter than it should usually be, or have a different amino acid that would somehow change the structure or the formation of the protein.  And so by not only filtering the sequence comparison between the parents and the child against the general population that is unaffected by this disease.  You can also look for the types of changes, whether there would be deleterious or not or sort of causing problems or not.  And that can help, as Jimmy mentioned, narrow down the list of what maybe a disease-causing mutation or what may not be a disease-causing mutation based on how strong the impact is of that change to the end results of that sequence.

JIMMY : Yes.  So the same change in different parts of the genome can cause sometimes big effect and sometimes no effect.  When it’s causing no effects sometime it’s called silent.  Maybe we can use analogy of a car; in St. Louis we had a hailstorm and that caused a lot of damage to cars.  If the cars are hit a little bit on the roof and it causes a small dent,  I mean, you can still drive the car.  It’s not a big deal. But for some unlucky people, for example, if they land on the glass, it will crack it.  So that causes a problem.  Then I had a very unlucky friend who had hail like right at the juncture where the trunk opens.  So they have to change their entire trunk and that was a big deal.  So when a change like that happens, like on a genome, when it’s on like the hinge of the trunk, it causes a big problem.  So in the same way, in the genome, depending on where those changes are, sometimes it could… everybody has a lot of different changes on the genome.  Some of them actually cause some effect.  But then there’s a few of them that really sort of cause functional differences and often are ones that cause disease.  And those are the ones that we’re looking for and potentially are the ones that may cause this disease in these kids are hoping to help.

MARISA : Another thing to mention is that for a lot of sort of traditional methods of looking at genome-wide for genes that are associated with disease, a lot of times it requires very large family pedigrees and large cohorts of patients in which there are high numbers of both affected and unaffected patients.  The benefit of sequencing is that you don’t need as many family members or as many affected individuals in order to still potentially get useful information.  So just by sequencing the parents and the child, it can potentially be enough information in order to try and identify a disease-causing change.  And that’s one of the benefits compared to some of the traditional methods that require a large population and specifically for diseases that are rare, or where there aren’t other affected family members, where the disorder is unique to just a single member of the family.  These types of advancement in technology can be very useful.

AMY : Thank you.  ”And how long does this genetic testing take?”

NAIRA : For the analysis stage, it’s a very long time.  And when you think of the analogy that Marisa and Jimmy were telling, it really depends on how obvious the difference is.  If it’s very obvious, think of the cars in the hail.  If it’s very obvious that you have a big damage to the crust, then it will be easy to find.  If it’s not very obvious, you’re going to have to look a little longer.  So it can take up to one year.  And it really depends on how obvious the mutation is.  Now, if you’re missing a very big chunk of your DNA, it might be easier for the scientist to find it.  The way the process is structured, you schedule an appointment with a clinical geneticist and it usually takes about two to three to four months to get an appointment with a clinical geneticist.  Sometimes, up to six months.  And after this clinical geneticist  determines you are a good patient for genome sequencing, and it’s likely that there’s a genetic component to what’s affecting your child, then it can take up to one year for the analysis to be performed.  And keep in mind that this analogy: if the mutation is very obvious, think of these cars that were in this hail.  If there’s a lot of damage to the roof of the car, it might be easy to see instead of a tiny little dent.

JIMMY : Yes.  What’s interesting though is that actual testing can be fast.  They’re predicting that by the end of this year, actually, to be able to sequence an entire genome for a $1000 in a day.  So theoretically, we can get the sequence in a day.  However, it takes a long time for you to see the doctor.  Patients know sometimes it takes a long time to go and see a doctor.  And then the doctor say yes and they will participate in the study, and then you wait for a space on the machine.  Once you switch on the machine, it takes a day.  But then, that’s only the letters.  That’s only the codes.  Then it takes time to decode that.  And like Naira said, sometimes if it’s really obvious, we can decode it very quickly.  Sometimes if it’s less obvious, it could take a long time.  And so it’s really variable.  And so the timeline  we’re using over in Rare Genomics, we estimate on average, from patient contacting us, seeing a doctor for the first time, during the project, it could take up to a year and we’re trying to make it shorter when we can and shorter as possible.  And hopefully we can shorten it.  And that’s one of our things that we’re trying very, very hard to do.  But a lot of advancement is going on.

NAIRA : One of the things to keep in mind is that the technology we’re developing to analyze the data is getting better, so the tendency for the data analysis portion of it is that the time can actually decrease with time.  Right now it can take about a year to analyze the data.  Maybe less, maybe more.  But the tendency is for this time to decrease.

AMY : Thank you.  We have another question, “If a family has an idea of what kind of gene is causing the problem, why do they recommend doing whole genome sequencing anyway, and what is the benefit of the sequencing?”

MARISA : So the benefit of sequencing in this case is actually to confirm that the gene that is suspected of being involved with this disease is actually the one that’s mutated or is causing the disorder.  And so sequencing can be used to confirm this mutation, and that can be very helpful in confirming the diagnosis and confirming a specific gene that is involved.  In some cases there can be a disorder where there are multiple genes in which a mutation, any one of those genes may cause particular disease and symptoms.  In other cases it may be a mutation in just one gene that is really causing the disease, for another disorder.  So one thing to be aware of is that as we’ve been mentioning, while the sequencing itself can be rapid, it’s the interpretation and the identification of what’s actually causing disease that can be challenging.  In some cases, even with rare diseases, what can be helpful is if there have been previous patients that have had similar symptoms and medical issues that also have a mutation in that gene.  That can help establish that particular gene as being causative of that disease.  But in other cases, it may not necessarily be fully possible to definitively identify which gene may be causing the disorder and some other research or investigation may be needed to further characterize these genes and try to identify which genes may be causing these symptoms and the characteristics of the disorder that are being done.  But what I would say is the main advantage to knowing what specific gene it is as compared to sort of a generalized idea of what kind of gene there’s a problem with is, if there is no treatment available or if there is treatment available, treatment available may be dependent on what the specific mutation is, or there may be some research options or treatment possibility  options that would be very dependent  on knowing specifically what gene is being impacted.  So we feel that it is as important as possible to try and identify this specific gene even if the current state of research doesn’t represent options for treatment.  Just knowing that information could be helpful in further advancing research as well as the advancement of further treatment options.

JIMMY : So for this patient or family who’s asking this question, maybe they think that they already know what the gene is.  I think the recommendation of — again, the disclaimer that we’re not offering medical advice, but for our patient, I think a doctor would often — so this is not advice — a doctor would often as he tries to sequence that gene particularly first, to see whether that’s the gene that caused the disease.  And very famous example, hemophilia.  There’s a specific gene. Or sickle cell, or cystic fibrosis. He would start off by testing that gene.  And that’s often for a lot of these diseases that that gene is what’s wrong.  But for a lot of — even for these diseases with a known gene, often, people would turn out negative for that.  And then you would have to sort of figure out what other genes are potentially causative.  For example, Rett syndrome, it has whole bunch of possible genes that potentially could be causing it.  Right now I think about two or three potentially — but then still a large population is negative for those genes.  So in those instances where we really haven’t sort of found what gene that’s broken, a wider sequencing effort is often helpful and what is traditionally done is they do a gene panel.  So a group of maybe 10, 20, sometimes maybe 30 genes that are also sequenced, either in serial or in parallel.  But now it’s almost more cost-effective to sequence the whole exome, or tens of thousands of genes at the same time.  So that’s definitely a decision to be made by a doctor, but single genes — if they think it is a single gene potentially, a doctor could just test that one first.  And if that’s a negative, to have sort of larger and larger sets.

AMY : Great.  ”Where can grant money be found for research, and how can people connect with researchers?”

NAIRA : Now that’s a great question and that’s what RGI does.  That’s why we founded Rare Genomics Institute.  We want to connect families with scientists and clinical geneticists who have the ability to offer genome sequencing, exome sequencing, for families who can use it for diagnostic purposes.  There are many different ways that you can pay for the project, and depending on the site, it might be eligible for grant money.  Grants are written in very specific ways, and sometimes they may cover of a particular type of disease.  Let’s say, a grant may cover a blood-related disorder, and it may cover a more specific disorder.  But not every grant will cover every case.  There are many other ways of paying for it.  Some commercial insurance companies have been reimbursing families for sequencing.  This is very new and we’re always very afraid of promising a family that they can get reimbursement from commercial insurance because this is just happening right now.  One of the things we have done as a non-profit organization is set up a crowdfunding page on our website.  And if you don’t know what crowdfunding is, go to Rare Genomics page on the Internet, and it’s raregenomics.org, and then you click the link that says “Our Patients.”  By clicking on that link, you can see some of the families that we have been able to help by crowd funding resources to pay for the genome sequencing projects.  Some families have approached us and they have said, “You know, I can pay for it myself.  I just really need your help finding the scientist and finding the clinical geneticist that can give me access to this technology.”  So that’s one of the things we do and that’s one of the things we’re good at — connecting families with the people who have the ability to do this for them and who are like, ahead of the technology.

JIMMY : I think what we hoped, really, is either this kind of service can be covered by insurance or there are existing grants for that.  But the reality is a lot of people aren’t eligible, but they still want to get this done.  And some people are able to pay but I think that’s sort of a smaller minority and we don’t want people to mortgage houses and sell cars, and that’s why we thought of this idea of crowdfunding as something very exciting where we can set up a page for a patient, and then you can tell your friends through social media, through different things, and everybody gives a little.  And together, right, it’s cheesy, it takes a village to raise a child, the cheesy sort thing that we say.  It takes an entire community to do research for a child as well.  So if everybody gives a little, then the entire community feels like they want pitch in a little bit, and then we can sort of fund research in that way.  So crowdfunding is a method for if other methods don’t work and people really want to do this for their kids, and that’s the method that we are facilitating for that to happen.

AMY : Great.  And we thank you for that.  ”So what happens if something is found and no one has ever seen that disease before?”

NAIRA : I think that one of the exciting things about Rare Genomic is that we have this extensive network between scientists and clinical geneticists.  And one of the things that get the scientific community very excited is when they feel that they can help someone.  Like, scientists want to work on problems that are meaningful.  They want to be able to answer questions that will help you, that will help the family.  So if you identify something on the genome that’s the cause of the disease and no one has ever had it before, then RGI can help you get connected to scientists and physicians who may be able to help you.

AMY : OK.  ”How many patients get a diagnosis from sequencing?”

JIMMY : Yes.  I mean, that’s a hard thing to say in terms of actual numbers.  But right now, within the scientific community, between 25 and 33%.  We usually estimate within a quarter to a third of people can get some sort of diagnosis.  And of those, actually, only a small minority of them actually gets some sort of treatment right away.  So we don’t want to over-promise people that this is going to be sort of the silver bullet and their child is going to get well right away, but it does provide some sort of a hope in advancement where other methods have failed.

AMY : OK.  So how about we look on our Facebook page and see if there’s any questions on there.  Jimmy, can you take a look and see what that question is?

JIMMY : So people who have questions, again, go to our Facebook page, to just remind people that that’s www.facebook.com/raregenomics. Rare Genomics is spelled r-a-r-e-g-e-n-o-m-i-c-s.  Raregenomics.  And then you can post the question there.  And then hopefully we’ll — if it’s sort of a general question, we’ll be able to answer it.  So let’s take a look.  There’s one question specifically about LEOPARD syndrome.  Maybe we’ll get back to that.  The question here is, “What is the difference between exome sequencing and mitoexome?”  Hmmm…

MARISA : So I assume that mitoexome refers to mitochondrial DNA sequencing.  I believe there’s a recent publication about this at the beginning of the year about the potential use as well as possible challenges of sequencing mitochondrial DNA.  So there — I want to go and take a look — there’s a difference between exome and mitoexome.  I’m not familiar with all the details of mitoexome sequencing but what I can share in general as far as mitochondrial DNA is that that’s something — so there’s DNA in the nuclei of ourselves.  There’s also mitochondrial DNA which is typically inherited from the mother.  And that is something where there has been a small number of diseases that have been identified based on mutations in mitochondrial DNA. I would say that is as far as my knowledge, I believe that exome and whole genome sequencing is something that has been gaining speed and is being used more than mitochondrial sequencing.  But perhaps I can let Naira and Jimmy, some of the other experts on the panel, comment a little bit more about this.

JIMMY : Yes.  So the mitochondria is a small organ within a cell.  They thought maybe they used to be another sort of tiny cell, but they actually reproduce themselves and they help produce energy in the cell, and they have their own DNA.  And for some diseases actually, it’s caused by problems in the mitochondria so then mitoexome sequencing is sequencing the exome (correction: AND) the mitochondria.  The mitochondrial DNA is much smaller so actually for some diseases, they sequence the mitochondria pretty regularly.  So sequencing the mitoexome, specifically at looking at diseases that potentially are in the mitochondria (CORRECTION: and) the exome versus generic exome sequencing which is the — sort of the exome of the human part of it.  So that’s what the difference is.  And mitochondrial sequencing, because it’s much smaller, it’s actually much easier and has been done in a clinical context much more pervasively than whole exome sequencing.

AMY : Jimmy, this is Amy.  I’d like to jump in and ask a quick question on that.  As you said, is there any potential in those two testing being available in one test, versus doing it separately?

JIMMY : Yes.  I mean, that’s a good question.  It depends on the design.  What scientists are doing these days — exome sequencing is, they design little beads and this thing with little beads have like special velcro on them.  This velcro is able to sort of stick to the part of the genome that is exome.  So what you need to do is when you design these little beads with velcros is also capture the mitochondria exomes.  It’s very feasible and it has been designed that way.  Just currently it is not being designed that way, but you know, there’s no reason why not the future, people can do that.  Right now, most of this is done as sort of two separate tests, the mitochondrial sequencing and then separately the exome genome sequencing or whole genome sequencing.  Another thing, too, is actually you have a lot more mitochondria in your body. Every cell has a lot of mitochondria.  There’s actually a variety of population.  So there are different techniques actually.  Sequencing the mitochondria versus a nuclear genome.  So there’s a little bit of difference there, too, and potentially that’s why it’s split up into two separate tests.

AMY : OK.  Thank you.  So I don’t see any other questions posted on the Facebook page.

JIMMY : Maybe we can go to the other questions that we haven’t got to, that people submitted beforehand.

AMY : OK.  Let’s see if we can go to those.  So one question is, “How do we set up a medical record for an undiagnosed patient when their health is ever-changing?”

JIMMY : Yes.  I mean, the medical record is going to be very, very important.  And I think Naira has talked to a lot of patients about this. I think the doctor only knows as good as — they only get one snapshot, seeing the patient.  And they rely very, very much on the medical record.  So one of the first things that we tell patients when they do come to us and they’re trying to do something very extensive, is to organize their medical records.  And actually, Amy, you could jump in here. You’ve organized medical records like a pro, right? What have you done for medical records?

AMY : Yes.  There’s a few things out there that can be used.  There’s some binders that families are using to help with just having the basic information to carry on to each doctor’s appointment.  And then families choose different methods of keeping the records of all past appointments, but I do advise that families ask for their copy of the reports as they go to the doctors because sometimes we might catch something that we didn’t catch at the doctor’s appointment.  So it’s good practice to get all those medical records that you can of families’ undiagnosed individual.  And then some families like to collect them by date and others like to collect them by service provider.  So it’s a matter of getting the records as the first priority and then how you organize them can be up to their personal decision.

NAIRA : Getting the medical records organized can help your clinical geneticist so much.  And the more you help your clinical geneticist, the more you help yourself.  Every time I help a family get an appointment, the doctors review those records very, very closely.  And they want to know about you.  They want to know about your child.  They want to know about the history of how the symptoms of the syndrome have manifested and they look in that information for clues.  What I was talking about earlier, the data analysis, is when the scientists are going through the data say, “If they have some clues on what to look for, the whole process is faster.”  He could potentially — you could potentially find the answers sooner.  So one of the first things that I tell families immediately after I connect them with a clinical geneticist is to get the medical records together and get as much information as they possibly can, bring them to your clinical geneticist, and have a discussion, have a frank discussion with them and that data could be used to help you and your family find an answer.

AMY : Thank you.  That was a great answer.  Just another question, “What resources are available to help people with rare and undiagnosed diseases find opportunities to participate in research?”

JIMMY : Yes.  I mean, that’s a good question.  And the difficulty is that there are so many different diseases that are out there and finding a specific research study for that is hard.  Actually, recently, last year, an organization contacted us.  Research Match, for example, is able to be a sort of clearing house to match different people.  The NIH, I would think, the Office of Rare Diseases, and there’s a specific research network that you can then look whether your particular disease is one that’s being researched.  And take a look there.  And then Office of Rare Diseases also has a database called GARD, G-A-R-D that sometimes has a link to that.  And then lastly, the European Registry actually has some good resources there.  European Registry’s organization is called Eurodis.  E-u-r-o-d-i-s.  And then their database that a lot of people use called the Orphanet.  It’s O-r-p-h-a-n-e-t.  Orphanet.  And sometimes Orphanet will have links for the specific diseases and then you might be able to find research opportunities there as well.  And actually, Amy, you actually know about the resources since you do a lot of research for this.

AMY : There’s not a whole lot of resources out there actually.  Some of the old ones that I used to use aren’t available anymore.  So I think you pointed out some of the biggest resources there.  And this information resources are constantly changing with just the different options out there for families like the UDP that’s come out and that’s a great resource.  Just for having opportunities for families.  So there’s really not a lot of resources.  I’m hoping that there will be some more added, and RGI is an added resource and of course SWAN USA is a good  resource for families who are trying to find information —

JIMMY : Yes.  I forgot to mention two very important organizations myself.  Of course, NORD, a national organization of rare diseases, and Genetic Alliance.  Genetic Alliance is great for groups wanting to set up new groups for that.  And NORD also has been great in terms of pushing for advocacy.  And then one more — we have — there was one question that we haven’t gone to, I just sort of skipped to, about a database for gene tests.  So, yes, there’s NIH site called Gene Tests, and you can just Google that.  And you can look at the different tests that potentially could relate to your disease.  And mostly, it’s actually used by doctors, but if you’re interested in that.

AMY : Great.

JIMMY : Let’s do one more question.  How’s that?

AMY : OK.

JIMMY : Before we end.

AMY : OK.  One more question.  Do you want to pick one more question or do you —

JIMMY : No.  You can pick.

AMY : OK.

JIMMY : Let’s get to the other ones.  Just for people who are on — who have submitted questions that we don’t answer, we’ll eventually answer them.

AMY : OK.  Do you think anyone can answer this one — “When and how is a rare disease or rare genetic disorder named?”

JIMMY : Yes.  I mean, multiple people have asked us this.  And it really depends on a lot of things.  So some diseases for example, are named by the process that caused it.  For example — let’s talk about PKU for example. Phenylketonuria.  In the urine, there’s phenylketones, that’s the name, sort of the descriptive name — but interestingly, if you’re overseas or are actually in Europe, it’s actually named after the discoverer, in terms of that disease.   So even from sort of between country and country, the name could be different.  Sometimes, it’s named after a patient.  Sometimes it’s named after the doctor who’s found it.  Sometimes it’s named after the region that the disease is discovered in as well.  So there’s no sort of — I think it’s as personal as parents naming their kids.  Sometimes researchers just name the disease as they find it.  So I think hopefully that — those are some of the reasons — no, ways that people are able to name diseases.

AMY : Thank you.  I think a lot of families often feel like their child’s condition, could be named after their child because they’re the one and only one with their kind of specific signs and symptoms.  So we often use in our community that our child has “their-name” Syndrome, after their name.  We often do that in our community.

JIMMY : Well, in the future, I mean, ultimately, everybody’s sickness is going to be very, very individualized and different, and really, all medicines should be individualized and personalized.  So maybe that is the way to think about it.  It’s a group of diseases but then really, it’s just like in cancer, for example.  I mean, they’re personalizing cancer.  So it’s not just breast cancer, it will say it’s Mary’s Breast Cancer.  Or it’s Sarah’s Breast Cancer.  So maybe you can think about rare diseases in that context.

AMY : Great.  OK.  Well, I thank everyone for joining us.  It’s been a great call today.  And we will be looking into seeing how this went and seeing as we might provide more conference call in the future.  So thank you for calling in.  Have a good evening.

JIMMY : Thank you.

AMY : Ba-bye.

NAIRA : Thank you.

MARISA : Thank you.

[End of Audio 00:58:32]

We’re going to be working with the intern team at 2e Creative this summer and into the next year, working on our branding and marketing and how we want to portray ourselves! Cannot wait to work with these great people.

Our press release is out on PRWeb, and All Things D, MassGenomics, and Genome Engineering have covered us today! Thanks to all of these great publications in getting the word out about our assistance to all of the Maya’s out there with no where else to turn!