In January 2019, the CMT Research Foundation began funding a research project led by Dr. Kleopas Kleopa at the Cyprus Institute of Neurology & Genetics to study a gene therapy approach to lower levels of PMP22 protein, which is the protein coded for by the gene that causes CMT1A. Dr. Kleopa is one of the world’s leading researchers in CMT. He and other scientists believe that reducing PMP22 levels may prevent people with the CMT1A gene from ever experiencing symptoms and possibly reverse some nerve damage in those whose CMT1A has already progressed.
Most recently, Dr. Kleopa and his team reported that their candidate therapy showed a substantial reduction in the PMP22 protein in the peripheral nerves of mice with CMT1A, along with improvements in nerve myelination and the ability of the nerves to conduct electrical impulses. Most importantly, the therapy improved strength and coordination in the mice.
After demonstrating tremendous progress during the past two years, the CMT Research Foundation’s Scientific Advisory Board has decided to extend funding for this project for six more months. The investment will support additional experiments to provide useful pre-clinical information needed for further development by biotech and pharmaceutical companies as well as potential clinical trials — both critical markers of research progress.
Additionally, the researchers will analyze neurofilament light (an emerging biomarker for CMT) and other proteins in the blood, along with skin biomarkers. Biomarkers are medical signs that indicate a particular therapy or drug is working. Understanding how these biomarkers change with treatment in the animal models will be key data to inform possible later human studies.
If successful, this project could lead to the first genetic therapy for CMT1A.
Summary of Project Results to Date
As of February 2021, Dr. Kleopa and his team have made impressive progress. First, they designed and tested several genetic sequences and viral vectors in mice genetically engineered to model CMT1A. The resultant genetic therapy reduced PMP22 levels by approximately half in the sciatic nerve and nerve roots one month after treatment.
The researchers then proceeded to a therapeutic trial, treating two-month-old CMT1A mice with the therapy for four months. The animals receiving the treatment showed improved strength and movement abilities. Additionally, their sciatic nerves had improved structure and were able to carry electrical signals more rapidly. A therapeutic trial in older mice, to model treatment in adults, showed similar improvements.
