By: Keith Fargo, Chief Scientific Officer, CMT Research Foundation

The CMT Research Foundation is proud to announce a new research collaboration with renowned nerve disease expert Dr. Rudolf Martini of University Hospital Würzburg to investigate whether inhibiting inflammation in the peripheral nerves could reduce symptoms and improve outcomes for patients with Charcot-Marie-Tooth disease Type 1B.

For people with CMT1B, mutations within a gene called myelin protein zero, or MPZ, cause dysfunction in the myelin sheath — the insulating structure around axons, which are the parts of the nerves that conduct electrical signals back and forth between the brain and spinal cord and other parts of the body. When the myelin sheath is functioning well, these signals travel rapidly. But when it begins to break down, the body’s communication system is impaired, leading to muscle deterioration and sensory problems in the feet and hands.

CMT1B is not only associated with the loss of myelin, but also with the eventual destruction of axons. In recent years, research has implicated inflammation as a culprit in this axon dysfunction. Nerve inflammation can activate a type of white blood cells called macrophages. Normally, macrophage activation is healthy, because these cells can rid the body of microbes, cancerous cells and other damaging materials. However, in CMT1 subtypes, the macrophages appear to attack the myelin and axons in the peripheral nerves. While this process is not yet fully understood, the macrophages appear to be activated through a protein called colony stimulating factor 1, which is sensed by a receptor on macrophages, known as CSF1 receptor (CSF1R). Previous studies indicate that blocking, or inhibiting, CSF1R activity reduces axon damage in animal models of other CMT forms, such as CMTX. Now, research is needed to test whether macrophage inactivation through CSF1R inhibition will show similarly positive results in an animal model of CMT1B (generated by Drs. Laura Feltri and Larry Wrabetz, for the University of Buffalo).

A Closer Look at This Research

In this newly funded CMT Research Foundation study, Dr. Rudolf Martini and his research team at University Hospital Würzburg will test whether inhibiting macrophage activation will prevent axon loss in an animal model of CMT1B. The research will be carried out in four stages:

• Stage 1: Comprehensively quantify and characterize the macrophages in the peripheral nerves of the animals with CMT1B.
• Stage 2: Treat young animals with a CSF1R inhibitor to see whether this will prevent the loss of axons.
• Stage 3: Treat adult animals with a CSF1R inhibitor. This is important because in many cases, a person may not know they have CMT until adulthood. It is important to find treatments for all people with CMT, not only those who are diagnosed early in their lives.
• Stage 4: Study the effects of treatment interruption, which is important because in real world settings, people may need to stop treatment or miss doses for a variety of reasons.

If successful, this research will provide important proof of concept that preventing inflammation by blocking macrophage activation pathways is a potential treatment for people living with CMT1B.

Learn more about all the research we’re currently funding.

Help Advance CMT Drug Development

While no treatments or cures currently exist for CMT, the science to change that does. Your donation to the CMT Research Foundation will fund cutting-edge research that’s solely focused on drug development. Together, we can change the course of CMT during our lifetime — and for every future generation.