DR. KLEOPAS KLEOPA
Dr. Kleopa’s research focuses on developing and studying mouse models with mutations in the SH3TC2 gene, which is linked to Charcot-Marie-Tooth disease type 4C (CMT4C). In CMT4C, mutations in SH3TC2 disrupt normal nerve function, leading to the symptoms of muscle weakness, atrophy, and other challenges associated with the disease.
By creating mouse models with similar SH3TC2 mutations, Dr. Kleopa’s research team can study the effects of the gene mutation on peripheral nerves. These mouse models are valuable because they help researchers observe the progression of CMT4C in a controlled environment, allowing them to see how nerve degeneration occurs over time and identify key molecular mechanisms involved in the disease.
The ultimate goal of Dr. Kleopa’s work is to use these models to test potential treatments, including gene therapies, which might repair or compensate for the defective SH3TC2 gene. By doing so, this research could pave the way for therapies that may slow, stop, or even reverse the nerve damage caused by CMT4C.
DR. ANNE-SOPHIE LIA
Dr. Anne-Sophie Lia and Camille Loret in their lab in France used CRISPR to create the first human stem cell model of CMT4C. This model expresses the actual mutations that 4C patients have (right now, they are focused on two of the most common premature stop codon mutations, Arg954 and Gln74), unlike the mouse and rat models which are just knockouts that are missing the protein entirely. Their lab plans to use this technology to test existing drugs that could work to treat CMT4C.
DR. ANDREAS ROOS
Dr. Andreas Roos has worked for years in Germany on understanding the basic biological mechanisms behind CMT4C. He made a major discovery, which is that SH3TC2 levels can be measured in patients' white blood cells. This is not true for most other types of CMT. It provides a powerful and simple biomarker (previously you would have to measure this with patient skin biopsies) and more importantly it means that patient blood can be used as a tool to screen existing and new therapeutic compounds to see if any have an effect on SH3TC2. He is already planning to do this work and focus on compounds that are already approved and on the market, which would significantly speed up the path to approval.
DRS. BURCAK OZES AND ZARIFE SAHEN
At Nationwide Childrens' in Ohio, Drs. Burcak Ozes and Zarife Sahenk presented a novel gene therapy in CMT4C. Instead of using a gene therapy to replace SH3TC2, they use a more generic gene therapy to stimulate the production of a protein called NT-3. NT-3 seems to promote the survival of Schwann cells, and development of axons and the myelin sheath. Testing their gene therapy in the CMT4C mouse yielded good results on the rotarod, grip strength, and nerve conduction velocity testing that they say is similar to Dr. Kleopa's results with his therapy.