WHAT IS CMT?
CMT, also commonly called hereditary sensory and motor neuropathy, is a genetic disease in which parts of the nerves become damaged and messages that run along the nerves move more slowly. Over time, this causes muscles in the feet, legs, and hands to lose strength and waste away (atrophy). Often, the muscle loss happens unevenly, which can cause physical deformity. There is no cure for CMT, but there are therapies that can help treat the symptoms.
WHAT ARE THE RISKS?
It's possible to be carrying CMT and not be aware of it. Awareness is vital because if you have the gene for CMT, whether you're symptomatic or not, the effects of neurotoxins may be detrimental to your health. View neurotoxin list here.
The Hereditary Neuropathy Foundation is dedicated to finding treatments and a cure for Charcot-Marie-Tooth (CMT) and related hereditary neuropathies while providing support and extensive information for those living with CMT and their families. HNF promotes and supports innovative therapeutic driven research.
what we have done
HNF is a leader in funding research that promotes accelerated discovery by establishing a collaborative research process that has defined goals for each funded lab and requires the sharing of discovery at each stage of research.
This multi-tiered approach will help people with CMT live a better life while we develop effective therapies, treatments, and a cure for CMT. We have developed the expertise with talented partners required to move towards clinical trials to bring effective treatments to the market for CMT.
This past year Therapeutic Research in Accelerated Discovery (TRIAD) Program completed the development of two assays for CMT1A caused by a point mutation or a duplication. High throughput screens are under way using the assay with proprietary libraries of thousands of compounds at the University of California, Los Angeles (UCLA) in collaboration with our funded lab at University of Southern California. It is very promising and we will provide updates periodically.
We also fund University of California - Davis for the development of a animal model for CMT 2A. To date there is no ideal animal model for testing therapeutics. We have committed additional funds after an in debt scientific review to fine-tune the mouse and believe our researchers will accomplish this task in early Spring. This will be groundbreaking! We will update you as soon as the mouse is ready. Distribution of our mouse models by Jackson Laboratory will greatly facilitate the access of these important research tools to the biomedical community, ensuring genetic quality and when at all possible, a minimum of legal restrictions. We will make the mouse readily available to eliminate the challenges to finding a cure for CMT. By removing hurdles to their widespread by academics and industry researchers we will engage the science community to develop more needed research
We are so confident in our team that HNF is launching the first of the year the Global Hereditary Neuropathy Registry to prepare for clinical trials. This registry is co-funded by Hannah's Hope Fund and in collaboration with Patient Crossroads a premier patient registry company. Stay tuned.
what we plan to do
HNF will add to its collaborative program leading research labs that specialize in technologies capable of elucidating the root cause and pathways leading to CMT and utilizing the information to identify drugs that can treat or cure CMT. One specific program we are initiating is to generate stem cell derived models of the disease using induced pluripotent stem (iPS) cells. These special stem cells can renew indefinitely and can differentiate into all cell types of the human body. These cells enables researchers to access unlimited amounts of the specific cells of interest affected in their disease of interest.
Using a genetic "tool", researchers can turn skin or blood cells from CMT 1A patients into iPS cells and subsequently the cells affected by the disease, neurons and their myelinating Schwann cells. Creating these cells from patient specific iPS cells allows researchers to replicate many of the events that occur in disease progression, as they carry the same genetic information as the patient. In order to bring this revolutionary technology a step further in the CMT research community, HNF will partner with two leading stem cell laboratories to generate numerous iPS cell lines, iPS cell derived Schwann cells, and identify the cellular causes of CMT. Our partnering laboratories have significant experience differentiating iPS cells into Schwann cells and scaling-up and standardizing production for drug discovery that is required to move this research toward a clinical intervention.
HNF is excited to use its collaborators' state of the art technology and deep experience with neurological disease research in order to ensure HNF's research dollars are optimized by funding research with the greatest potential to actually find treatments.
In addition, we will develop a research model to examine the benefits of exercise, with and without neurotrophic therapies (drugs or genes that target nerves), in the treatment of CMT. Our novel research will be carried out through a cooperative venture of leading researchers at the West Virginia University (WVU) School of Medicine, the National Institute for Occupational Safety & Health (NIOSH), and the Max-Planck Institute for Experimental Medicine. We will take experimental rats (provided by the Max Planck Institute), which have been genetically modified to have CMT, and exercise them on a specialized resistance-type training machine, called a dynamometer (developed at NIOSH). The animals' exercise routine will be very tightly controlled, including all the training variables, such as the volume (sets and reps), intensity (how hard), duration (time per training session), frequency (number of training sessions per week), and progression (training variable increases) of exercise. Upon completion of the training protocol, the scientists will determine the extent to which the animals have beneficially adapted to the exercise training. To do so, our scientists will analyze exercise-induced:
Over the course of these experiments, the exercise will be refined to identify the type, quantity, and frequency of training that provides the greatest benefit to these CMT animals. Once the determination has been made as to how best to formulate the most effective exercise prescription, the research model will progress to human trials, and the study of CMT-specific exercise will begin in CMT patients. Furthermore, in the not-too-distant future, the scientists will look to combine the exercise with other agents (like drugs or gene therapies), to establish if the combination of exercise and other forms of treatment are more effective than exercise or other agents used alone.
These comprehensive results will also be used to determine how beneficial adaptations to muscles, nerves, genes, proteins, and biochemicals are related to each other. If, indeed, such relationships are discovered, this may very well provide great insight into how genes and proteins "talk" to each other in response to an exercise stimulus, either alone or combined with drugs or gene therapies. Such a discovery may very well allow scientists to understand the mechanisms that control the exercise response (with or without additional agents) in CMT patients. We are very optimistic that this unique, novel, and cutting-edge research will, at the very least, eventually provide allied health practitioners with additional, validated clinical options to manage and treat patients with CMT.
Your donations are always welcome and will fund important CMT research efforts in the coming year.