WHAT IS CMT4J?
CMT4J, or Charcot Marie Tooth, Type 4J, is a severe form of Charcot Marie Tooth Disease. Charcot Marie Tooth disease is the most common hereditary neuropathy, affecting about 1/2,500 people in the U.S. CMT is an umbrella term, encompassing many different forms of CMT with a very wide variation in onset, symptoms and nature of inheritance. CMT is also known as hereditary motor and sensory neuropathy (HMSN). CMT affects the peripheral nerves in the body–those that lie outside the brain and spinal cord, supplying muscles and sensory nerves. One of the many subsets of CMT, CMT4J is considered to be ultra-rare.
HOW DO PEOPLE GET CMT4J?
CMT4J is an autosomal recessive disease, caused by a mutation on the FIG4 gene, located on chromosome 6. Usually, the parents of a person with CMT4J are both carriers for the FIG4 gene. Most autosomal recessive diseases tend to have great variability, meaning that the age of onset, severity and course of disease progression can be very different from person to person.
WHAT ARE THE SYMPTOMS OF CMT4J?
Some people with CMT4J can exhibit signs or symptoms of the disease from very early on–from infancy or toddlerhood. Often, walking is delayed and many CMT4J patients exhibit clumsiness, gait difficulties or weakness in early childhood. Sometimes CMT4J does not start until later in life.
Symptoms of CMT4J can include: mild to profound muscle weakness in either the legs or arms or both. Sometimes CMT4J can cause joint deformities and contractions in the hands and feet, which may require surgery. It can also cause looseness in the joints, making them more vulnerable to instability and dislocation. CMT4J has the capacity to cause profound, accelerating limb weakness and muscle atrophy. Patients can have difficulty walking, requiring the use of walkers, wheelchairs or other assistive devices. CMT4J can cause upper extremity weakness, making it difficult for people to use their hands or lift up their arms. As disease progresses, it can also cause weakness in the trunk, chest and neck muscles. Later, it could affect the nerves that innervate the diaphragm, making it difficult to breathe or take a full breath. Upper respiratory infections–the common cold and flu–can cause complications with breathing because of this.
Some scientific papers compare CMT4J with ALS (Lou Gehrig’s Disease). In fact, the FIG4 gene mutation is shared in common with a small percentage of people diagnosed with ALS, but currently it is not thought to play a role in ALS disease.
At present, there is no treatment or cure for CMT4J. But there is HOPE.
WHAT HAPPENS IN THE BODY BECAUSE OF CMT4J?
Scientists believe that the FIG4 mutation causes disruption in protein and lysosomal function. This disruption causes drastic changes in the cells, which in turn affect the nerves and neuromuscular junctions, causing degeneration and disruption in myelin formation and activity. Recently, scientists have started thinking about CMT4J as more of a Lysosomal Storage Disease.
IS THERE A TREATMENT OR CURE FOR CMT4J?
Currently there is no treatment or cure; however, many clinicians and scientists believe that Gene Therapy holds promise for a cure for CMT4J and many other rare diseases. Gene therapy has already shown success in other diseases and is currently being used in over 600 clinical trials throughout the world. We are truly on the cusp of enormous breakthroughs using gene therapy to treat and cure many diseases. Rare and ultra-rare diseases represent ideal diseases to treat with gene therapy, as most are monogenic (involving only one gene).
Cure CMT4J is on a path to test and use gene therapy to treat and cure CMT4J.
HOW CAN A POSSIBLE TREATMENT APPLY TO OTHER RARE DISEASES?
Rare diseases are surprisingly common! 1 in 10 Americans is affected by a rare disease, with 80% of them involving a problematic gene. The model that Cure CMT4J is pursuing was recently used to treat Batten Disease and Giant Axonal Neuropathy—also monogenic diseases. It represents a pathway to clinical trials that could possibly help the more than 7000 rare and ultra-rare diseases. Cure CMT4J represents Hope for so many other families.