Charcot-Marie-Tooth Syndrome

While there is no known cure for CMT, the Avicena Group is presently developing a novel drug candidate for the treatment of the disease. Results from a pilot study of the compound demonstrated a significant increase in muscle size, as well as in the level of total muscle creatine concentration. These findings indicate that treatment with the compound may lead to increased muscle strength and increased aerobic capacity, as well as an overall reduction in the severity of disease symptoms. The Avicena Group is currently planning to initiate additional studies of this compound for the treatment of CMT.

What is CMT
CMT is a heterogeneous disorder in which genetic mutations cause the deterioration of nerves responsible for controlling the muscles of the hand, arm, foot and leg. Characterized by the progressive degeneration of these muscles, CMT can manifest itself through symptoms that range from mild to severe deformities. The disease is typically not fatal and does not affect life span or intellectual ability.

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Types of CMT
CMT is classified into various subtypes, including 1A, 1B, 1D, 2E, 2F, X-Linked, and HNPP. These classifications are used to differentiate the specific genetic mutation responsible for the disease, the manner in which the disease was contracted, and the severity of the patient's symptoms.

While the most common subtype of CMT, CMT1A, is inherited in an autosomal dominant pattern, the remaining subtypes of the disease are classified as autosomal recessive or sex-linked.

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Symptoms of CMT
It is important to note that symptoms of CMT, as well as the degree of severity of those symptoms, may vary greatly from patient to patient, even within the same family. Each type of CMT is characterized by symptoms that range from severe to mild to unnoticeable.

The most common symptom of CMT is muscle atrophy in the extremities. Additionally, patients may experience a loss of sensory nerve function, as well as some impairment of nerve reflexes in the extremities. Other common signs of the disease may include abnormally high arched feet, flat feet, hammer toes, and poor hand coordination.

While symptoms of CMT are typically noticed in childhood or early adulthood, the disease can manifest itself at any stage in life.

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Progression of CMT
CMT is marked by progressive nerve degeneration and related muscle atrophy. As the nerves of the feet, legs, hands and arms degenerate, patients afflicted with CMT slowly lose the normal use of these extremities. One of the earliest signs of the disease is a high arched foot and as the disease progresses, additional structural foot deformities take place. In addition, frequent ankle sprains are common injuries due to these structural issues.

The progressive muscle atrophy associated with CMT typically leads to problems with walking, running, and keeping a balance. In rare occasions, muscle weakness may also extend to the upper legs. Hand function is also affected by progressive muscle atrophy, making fine acts such as writing and holding utensils increasingly difficult.

As the disease progresses into later stages, the degeneration of nerve function leads to sensory loss in the hands and feet. The ability to distinguish hot and cold diminishes, as does the sense of touch.

In most cases, the full expression of CMT symptoms occurs by age 30, with those patients diagnosed with CMT earliest in life exhibiting the most severe symptoms.

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Diagnosis of CMT
In order to diagnose CMT, a patient undergoes a series of tests that include evaluation of muscle atrophy and nerve condition, examination of muscle and nerve sensory responses, and electromyographic (EMG) studies. Additionally, a thorough review of the patient's family history with regard to CMT is conducted.

For the 1A and 1X types of CMT, a DNA blood test can provide diagnosis.

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Causes of CMT
CMT is an inherited disease caused by various genetic mutations or through certain hereditary patterns. While the most common type of CMT is caused by an autosomal dominant gene, the remaining types of the disease are classified as autosomal recessive or sex-linked.

It is important to note that some people who carry the CMT genetic trait show no apparent physical symptoms.

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Incidences of CMT
CMT is the most common inherited neurological disorder, affecting approximately 150,000 people in the United States. Due to the fact that CMT may easily be misdiagnosed, experts estimate that as many as 300,000 people may actually have the disease.

CMT affects all races and ethnic groups.

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Treatment of CMT
While there is no known cure for CMT, physical therapy and moderate physical activity have been shown to help maintain muscle strength and endurance in patients. In addition, custom shoes and/or shoe inserts may improve gait and leg braces may prevent ankle sprains and aid with walking. Furthermore, corrective orthopedic foot surgery may be needed to help maintain mobility. Research has also demonstrated that hand-specific exercises, adaptive devices, and surgery can all help maintain hand function.

The Avicena Group is presently developing a novel drug candidate for the treatment of CMT. Results from a pilot study of the compound, led by Robert D. Chetlin and Dr. Laurie Gutmann of West Virginia University School of Medicine, demonstrated a significant increase in muscle size, as well as in the level of total muscle creatine concentration. These findings indicate that treatment with the compound may lead to increased muscle strength and increased aerobic capacity, as well as an overall reduction in the severity of disease symptoms. The Avicena Group is planning to initiate additional studies of this compound for the treatment of CMT.

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