What You Need to Know about CMS and Clinical Trials
Why clinical trials are a crucial element in the path towards better treatment for Congenital Myasthenic Syndromes.
What Is CMS?
Congenital Myasthenic Syndromes (CMS) is a rare genetic condition caused by defective genes that affect the receptors at the neuromuscular junction (NMJ), where the nerves connect to the muscles. The interference at the NMJ, the point where the nerves signal the muscles to contract, results in muscle weakness that can affect the eyes, the limbs, as well as chewing and swallowing.
There are many faulty genes known to be associated with CMS, such as CHRNA, CHRNB, CHRND, CHRNE, CHAT, COLQ, RAPSN and MUSK, ChAT, COLQ, Rapsyn, LRP4 and DOK7. Those with ChAT and COLQ usually show symptoms at birth or early infancy. Blood tests with genetic typing establish the diagnosis of CMS, but it’s important to know which of the gene mutations are the cause of it. The gene mutation can determine the age it becomes evident, the course of the disease, and the response to treatments. It seems that the more common gene mutations are DOK7 and rapsyn, but there are no extensive studies that establish that perception.
How Is CMS Diagnosed?
CMS can be difficult to diagnose because its symptoms resemble so many other diseases. Surveys have shown that up to 80% of young children with CMS are misdiagnosed, while 94% of adults are misdiagnosed. The most common symptoms are droopy eyelids and facial muscles, especially in the first decade of life. In adults, CMS often causes weakness of the limbs and leads to misdiagnosis of autoimmune diseases like myasthenia gravis (MG).
Because CMS due to DOK7 mutations is a rare disorder, and difficult to diagnose, there have not been enough participants to fuel clinical trials investigating potential new treatments. Therefore, much of what is known about treating CMS derives from small studies from specific hospitals or clinics. From one such study center in Oxford, UK, adults diagnosed with DOK7 CMS, where signs and symptoms were first noticed under age 10, responded to treatment with pyridostigmine.
More information was gathered on the symptoms of and treatments for people diagnosed with DOK7 CMS from another small study, which surveyed 10 adults diagnosed with DOK7 CMS. This study found that although their symptoms might have been worse as children, they then stabilized for a time before becoming progressively worse. These people were able to manage their symptoms with ephedrine, but the response seemed to be better over time rather than immediately.
Why Are Clinical Studies About CMS So Important?
Unfortunately, as of now there are not many large studies or established research about the experiences of those who have been diagnosed with CMS—particularly people who may not have received a confirmed diagnosis or underwent their specific mutation as adults. As is the case with myasthenia gravis, neuromyelitis optica spectrum disease, or MOGAD antibody disease, more about CMS can be discovered via research studies, and particularly observational studies. These studies can provide more insight on the initial characteristics of the disease as well as its progression, and as a result new therapies can be developed. It is up to us to participate in studies that can shed light on the experiences of those living with rare disease, so that additional studies can be designed that reflect the reality of the human experience.
To get more information on clinical studies in CMS and find out how we can help, contact us.
SOURCES
Jagtap, et al. ‘Congenital myasthenia syndromes’,Ann Indian Acad of Neurol, 2013; 16: 3, pp.338-341.
Lashley D, et al. Neurology 2010;74:1517–1523
Palace J, et al. Brain (2007), 130, 1507-1515.