Streamlined diagnostic procedures, better data collection, a new clinical trials network and new laboratory research are the foundations of MDA's CMT program
It begins with weakness in the muscles of the lower legs and feet, causing frequent tripping and ankle injuries. Feet are often so high-arched that comfortable shoes can’t be found.
Hands also can be affected, making it difficult to hold a pencil, type on a computer or play a musical instrument.
Loss of sensation in the lower legs, feet, hands and forearms often occurs. Although not as troublesome as weakness in these areas, it can make simple tasks more daunting.
The problem underlying all these signs and symptoms is Charcot-Marie-Tooth disease, or CMT, named after the three physicians who first described it late in the 19th century: Jean-Martin Charcot and Pierre Marie, two French neurologists, and British physician Howard Henry Tooth.
Symptoms generally begin in childhood or adolescence, although onset can be as early as infancy or as late as adulthood. The disease is usually slowly progressive, with the majority of patients able to function without severe disability — albeit with some difficulties — all their lives.
Often, CMT comes with a family history. When multiple family members are affected, the symptoms, though they’re not generally welcome, at least are recognized and understood.
When there’s no family history of CMT, children displaying symptoms initially may be warned to “stop dragging your feet” or “pay attention to what you’re doing,” or they may be treated for conditions they don’t have.
CMT is a genetic problem in the peripheral nerves — bundles of fibers (also called axons) that run between the spinal cord and brain and the periphery of the body.
|A high-arched foot is typical in CMT.|
|Supportive shoes and lower-leg braces are helpful to many with CMT.|
Peripheral nerves transmit signals from the brain and spinal cord out to the muscles, making movement possible; and back from the periphery of the body to the spinal cord and brain, allowing sensations to be perceived.
Since the early 1990s, defects that can cause CMT have been identified in more than 30 genes, improving diagnosis and understanding of the underlying molecular mechanisms.
The genes involved (many of which were identified by MDA-supported researchers) carry instructions for proteins that affect various aspects of peripheral-nerve function.
In most of the various types of CMT, the primary problem lies in one of three places:
The myelin made by the Schwann cells winds around the axon the way paper towels wind around a cardboard tube. Among other functions, the myelin sheath insulates the axon and speeds nerve conduction along its length, just as insulation aids signal transmission through a wire.
If anything is amiss with the axon or its myelin sheath, motor and sensory signals can’t be effectively transmitted, especially over long distances such as between the spinal cord and the feet or hands.
MDA has been funding CMT research since the 1960s. As of the end of 2010, MDA had awarded more than $26.2 million to investigators in this disease and is currently supporting 22 CMT-related research projects.
Today, medical care for CMT remains mostly supportive, consisting largely of bracing and surgery for the feet. (See Surgery Sometimes, Bracing Often, Caution Always: Caring for the CMT-Affected Foot, in the September 2006 issue of Quest.)
Doctors and scientists gathering data from human and laboratory studies are rapidly adding pieces to the CMT puzzle. Research in CMT-related biology has allowed doctors to know more than ever about how nerve fibers work in health and disease, providing vital clues for development of new therapies (see CMT Science Today).
In addition, a new partnership between MDA and the National Institutes of Health (NIH) has led to an international network of centers to assess people with CMT and collect data, forming a crucial infrastructure on which to base future trials of new treatments. (See Providing a Network for Clinical Research in CMT.)
Today, the speed and accuracy of CMT diagnosis has improved markedly from just a few years ago; and disease-modifying drugs, while not yet available, probably aren’t far off.
The following sections present information about the latest in CMT diagnosis, research and clinical trials. For answers to specific questions about your own CMT diagnosis, talk with your MDA clinic team.