The US-based CMTA (Charcot Marie Tooth Association) has a 12-year-old program called the Strategy to Accelerate Research (STAR) that is actively pursuing the causes and possible cures for CMT. STAR will cover nearly all CMT Type 1s and 2s, including types with as yet unidentified genetic causes.
Helping the Most People First
Progression in all types of CMT occurs as the longest axons are lost, so developing chemical inhibitors of a recently identified biochemical trigger of axonal degeneration is a promising priority.
STAR is currently focused on:
- Genetic Therapies
- Drug Development
Attracting pharmaceutical companies to work therapeutic drugs for CMT has been a part of the CMTA’s advocacy work with STAR.
It’s not just about CMT
The Muscular Dystrophy Association (MDA) has been involved in CMT research because MD research is often relevant to CMT and other neuromuscular diseases. However, it’s important to maintain the distinction between CMT and MD, as they are two completely different diseases.
Muscular Dystrophy Canada (MDC) considers over 160 conditions as types of “Neuromuscular Disorder,” including Spinal Muscular Atrophy (SMA), Duchenne Muscular Dystrophy (DMD), Facioscapulohumeral MD (FSHD), Myotonic Dystrophy, Limb-Girdle Dystrophy (LGMD), Congenital MD (CMD), and Myasthenia Gravis.
MD and CMT both fit within this umbrella category of “neuromuscular disease.” How exactly they relate and differ is a topic I’d like to write about in the future.
Please contact me if you have some tips or opinions about these topics! 📬
I’ve also been trying to determine why MS and MD became so better known, diagnosed, studied, and treated than CMT, given their common origin in 19th century researchers and discoveries that laid the foundations for modern neurology. 🤔
A Summary of the Current Research
Here is a summary of my notes on CMTA, HNF, and MDA/MDC research news in 2018. Most (if not all) of it has to do with work supported by STAR/ I’ve tried to translate this material into simpler and clearer language with a minimum of technical jargon that’s explained in the links:
CMT1, X, and 4 (Demyelinating)
- CMT1A might be cured by silencing a gene (PMP22) that is overactive in Schwann cells.
- RNA interferences decrease PMP22 levels in CMT1A.
- Ionis Pharmaceuticals is working on antisense oligonucleotides (ASOs) which have reversed CMT1A symptoms in mice.
- Gene editing through CRISPR has been used to “reduce the expression of the gene PMP22 in nerve cells can improve nerve functioning and limit demyelination (damage to the protective covering that surrounds nerve fibers) in a mouse model of Charcot-Marie-Tooth disease 1A (CMT1A).”
- CMT1X and CMT4 are caused by defective genes that might be replaced.
- Dr. Kleopas Kleopa at the Cyprus Institute of Neurology and Genetics is investigating gene therapy for CMT1X and CMT4C.
- CMT1B could be cured by restoring the balance of myelin proteins and counteracting axonal degeneration.
- Approximately 50% of CMT2 patients do not have a definitive genetic diagnosis. Dr. Stephan Zuchner at the University of Miami’s Inherited Neuropathies Consortium has been working to improve diagnostic screening for CMT2.
- Research on CMT1 and CMT4 may be relevant to CMT2.
- As mentioned above, progression in all types of CMT occurs as the longest axons are damaged or lost. A biochemical trigger of axonal degeneration was recently discovered, so now new research and trials to develop drugs that inhibit this trigger are being pursued. This is likely to result in something close to a cure for people who are diagnosed and treated early in their life because it will prevent CMT from progressively disabling peripheral motor nerves. Slowing axonal degeneration even for older people will be a welcome result too!
- It may be possible to make and edit the genome for human neurons taken from the stem cells of people with CMT2A and CMT2E.
- Gene Therapy for Spinal Muscular Atrophy (SMA) might help with CMT2 because both involve the same motor neurons. Pilot studies on mice have been successful enough to lead to the first single-person trial in 2020.
- CMT2A is commonly caused by a mutation of the MFN2 gene which encodes the Mitofusin 2 protein. This protein is essential to the process of Mitochondrial fusion which protects and sustains the life and health of cells. Custom-designed molecules can stimulate the activity of mitofusin proteins, so this is being tested on mice. A possible future outcome of this research might be drugs that help people with CMT2A produce the proteins genetic mutations prevent them from producing.
What would you like to know about CMT research for cures and therapeutic drugs? Let me know in the comments.
Leave a Reply