The CMT Research Foundation is pleased to announce that Dr. Kleopas A. Kleopa and his team at the Cyprus Institute of Neurology & Genetics, Nicosia, have completed the third milestone of their 24-month CMT1A gene therapy project. CMT1A is caused by duplication of a region of DNA that includes the gene for PMP22, a protein that makes up a crucial part of the myelin sheath surrounding axons in the peripheral nerves.
In people with this duplication the gene is overexpressed and the peripheral nerves gradually deteriorate, leading to weakness, problems with balance, and deformities of the legs and arms, frequently becoming debilitating. The overall goal of this project is to test a virally delivered gene therapy for its ability to reduce PMP22 levels to normal in a mouse model of CMT1A and improve or even reverse similar outcomes.
During the project, Dr. Kleopa and his collaborator Dr. Scott Q. Harper at Nationwide Children’s Hospital in Columbus, Ohio, designed gene therapies with several different sequences and first tested them in cells in a dish. Using the best performing sequence, they then packaged the gene therapy in a viral delivery vector and gave it to rodents with CMT1A by injecting it into the fluid surrounding their spinal cords. The gene therapy reduced PMP22 levels in the peripheral nerve tissues by a substantial amount compared to mice who did not receive the therapy.
Furthermore, when the researchers examined the nerves of the rodents under a microscope, there were far fewer signs of demyelination, and indication that the genetic therapy was having a beneficial effect on nerve health. And most importantly, measurements of nerve function, strength, and balance all improved significantly, often to levels that made the treated rodents indistinguishable from rodents without the CMT1A-causing mutation. Strikingly, the gene therapy provided a beneficial effect both in young rodents and in older rodents who already had significant loss of strength and balance. Taken together, these data provide important proof of principle for a promising approach to treating CMT1A.
This brings the original scope of the project to completion, but as we alerted you in the most recent update, we have extended additional funding for this project to enable additional supportive experiments and analysis of biomarkers.
