What is Muckle-Wells Syndrome?
Muckle-Wells Syndrome is a form of cryopyrin-associated periodic syndrome (CAPS) that is caused by a mutation in the CIAS1/NLRP3 gene and the increased activity of the protein cryopyrin in the body. This leads to inflammatory damage throughout the body as well as several other symptoms, including the possibility of Amyloidosis.

What is the prevalence of Muckle-Wells Syndrome?
The incidence of CAPS has been reported to be approximately 1 in 1,000,000 people in the United States and Europe. In most cases, the genetic mutation is passed on for generations in families. There is a 50% chance that a parent with CAPS or a genetic mutation will be pass it along to his or her child.

How is Muckle-Wells Syndrome diagnosed?
There are multiple ways to diagnose Muckle-Wells Syndrome. Blood tests such as an erythrocyte sedimentation rate (ESR) could be taken to measure the degree of inflammation in the body, as an elevated ESR could indicate Muckle-Wells Syndrome. Other blood tests could be taken and analyzed as well to see if a patient has leukocytosis (an increase in the number of white cells in the blood), anemia (a deficiency of red blood cells or hemoglobin in the blood), an elevated C-reactive protein level (the level rises when there is inflammation throughout the body), and/or an elevated serum amyloid A level. Patients may also undergo a cerebrospinal fluid analysis, an audiogram, a kidney biopsy, a urine protein test, and/or genetic testing in order to be diagnosed.

Is there any specific gene/pathway in Muckle-Wells Syndrome that has been identified?
Muckle-Wells Syndrome is caused by mutations in the NLRP3 gene (aka CIAS1). This gene provides instructions for the production of the protein cryopyrin, which plays a vital role in regulating our immune system. When the body is injured or diseased, the immune system uses a process called inflammation to fight pathogens and facilitate tissue repair, and then inhibits the inflammatory response to prevent damage to its own cells and tissues. NLRP3 gene mutations are believed to result in hyperactive cryopyrin proteins. This causes an overproduction in interleukin-1 beta (IL-1β) proteins, which results in an inappropriate inflammatory inhibition. This can cause fever and damage to the body’s cells.

How is Muckle-Wells Syndrome treated?
There are currently 2 FDA-approved prescription treatments for the symptoms of MWS, both of which target the IL-1β protein. ARCALYST (rilonacept) is an IL-1β blocker injection for CAPS patients above the age of 12. ILARIS (canakinumab) is a monoclonal IL-1β antibody for CAPS patients above the age of 4. Anakinra is an IL-1β receptor antagonist has also been shown to lead to a decrease in disease activity, including an improvement in hearing loss.

These drugs help to inhibit the hypersensitive inflammatory response and relieve symptoms such as fever, joint pain, rash, eye redness/pain, and fatigue. However, it is important to remember that these drugs achieve this by lowering the immune system, leaving the body more vulnerable to infections.

Are there any clinical trials underway for Muckle-Wells Syndrome? 
Yes, the NIH is currently recruiting patients to study the effectiveness of a new drug, ACZ885, as treatment for MWS. More information on the clinical trial can be found here.

How can RareShare be helpful to Muckle-Wells Syndrome patients and families? 
The MWS Rareshare community has 94 members. There are currently 24 active discussions underway, helping to connect patients, health workers, caregivers and families interested in MWS and providing them continual access to community resources.

RareShare, MGCI Cancer Society and RG Chapter