CMTA and MDA Co-Fund Proof-of-Concept Study Using AAV Vector to Deliver Gene Replacement Therapy in X-linked Charcot-Marie-Tooth Disease

Kleopas A. Kleopa, MD, is head of Neurology Clinic E and Neuroscience Laboratory, the Cyprus Institute of Neurology. Dr. Kleopa is also a member of the CMTA Scientific Advisory Board.

Glenolden, PA and New York, NY, March 1, 2019 — The Charcot-Marie-Tooth Association (CMTA) and the Muscular Dystrophy Association (MDA) announced that they have jointly awarded a research grant totaling $276,430 over three years to Kleopas Kleopa, M.D., professor and senior consulting neurologist at the Cyprus Institute of Neurology and Genetics, Cyprus School of Molecular Medicine, in Nicosia, Cyprus. Dr. Kleopa is a world-renowned expert on gene replacement therapy for CMT1X, the second-most-common form of Charcot-Marie-Tooth disease (CMT).

Mutations in the gene coding for the gap junction beta-1 protein (GJB1), also known as connexin 32 (Cx32), are associated with the X-linked form of CMT (CMT1X), which affects approximately 1 in 25,000 people. Using this grant funding, Dr. Kleopa will perform critical, proof-of-concept studies to test whether delivery of the Cx32 gene using an adeno-associated virus (AAV) vector can improve symptoms in a mouse model of CMT1X as well as determine the optimal route for delivery of the therapy.

AAV vector technology has been shown to be a safe and effective delivery vehicle for “corrective” gene replacement therapy in both preclinical and clinical studies. There have been several successful applications of AAV vector gene replacement therapy for genetic diseases of the nervous system. For example, AveXis, a Novartis company, currently has a Biological License Application (BLA) under review by the Food and Drug Administration (FDA) for their gene replacement therapy for spinal muscular atrophy (SMA), which has shown encouraging results in a Phase 1 clinical trial.

“The study is yet another step on the road to realizing our hope that in the not-too-distant future, gene therapy for CMT will be a reality beyond the lab,” said CMTA CEO Amy Gray. “This project builds upon our prior joint efforts to take gene therapy for CMT1X to the next phase, but even more importantly, if successful, learnings will be applied to all demyelinating forms of CMT (type 1 and most type 4).” “Gene therapy continues to show promise for the treatment of neuromuscular disease,” said Amanda Haidet-Phillips, Ph.D., one of the MDA’s scientific portfolio directors. “MDA is hopeful that this new, translational work may pave the way for gene therapy to be developed for CMT and we are grateful for the partnership of the CMTA to help accelerate this important study forward.”

With previous MDA-funded support, Dr. Kleopa pioneered a gene therapy approach to treat the X-linked form of CMT, showing that a single spinal injection of the Cx32 gene was associated with production of normal protein in nerves and improvement of peripheral nerve health and motor performance in a mouse model of CMT. In a follow-up study co-funded by the MDA and the CMTA, he examined whether repeated injections in mice led to increased protein levels and tested whether treatment at later stages of the disease led to improvement like that seen for treatment in the early stages.

The target cell type for this therapy is the Schwann cell, which generates the insulating myelin sheath around peripheral nerves. The challenge for CMT1X and other demyelinating forms of CMT is optimizing delivery of the gene to Schwann cells. In previous studies, Dr. Kleopa employed a different type of viral vector to deliver the Cx32 gene, but for this new study he will adapt this approach to AAV, which has been more widely used in the nervous system and shown promise in clinical studies for other diseases. The project will test several types of AAV and different injection paradigms to determine the best method to restore the function of Cx32 in Schwann cells. Positive results may help advance development of treatments for other types of CMT affecting Schwann cells, as a similar AAV approach can be applied to CMT1A and other subtypes of CMT1.

Dr. Kleopa recently joined the CMTA’s Scientific Advisory Board, along with three other gene therapy experts, reflecting the field’s expanding importance in the search for a cure for CMT.

The MDA and the CMTA have been working together since 2016 to advance CMT research, therapy development and clinical care, and to increase understanding about the disease by improving education for children and adults affected by CMT, medical professionals, and the public.

About MDA

MDA is committed to transforming the lives of people affected by muscular dystrophy, ALS and related neuromuscular diseases. We do this through innovations in science and innovations in care. As the largest source of funding for neuromuscular disease research outside of the federal government, MDA has committed more than $1 billion since our inception to accelerate the discovery of therapies and cures. Research we have supported is directly linked to approved, life-changing therapies across multiple neuromuscular diseases. We support the largest network of multidisciplinary clinics providing best-in-class care at more than 150 of the nation’s top medical institutions, and each year thousands of children and young adults learn vital life skills and gain independence at MDA Summer Camp and through recreational programs. For more information visit

About CMTA

The Charcot-Marie-Tooth Association is dedicated to finding treatments and a cure for CMT, and to improving the quality of life for everyone living with the disease. The CMTA’s Strategy to Accelerate Research (STAR) brings top researchers together with pharmaceutical and biotechnology partners to accelerate scientific breakthroughs. STAR has one goal: to accelerate the development of treatments for CMT. Both research and treatment happen at the two dozen CMTA-supported Centers of Excellence at top-flight medical institutions nationwide. The CMTA also offers a number of community programs, including more than 70 local branches nationwide; Camp Footprint, the nation’s only camp exclusively for kids with CMT; and Patient/Family conferences, where patients can meet the researchers and clinicians working on their behalf. To learn more about the CMTA, please visit

Media contacts:

Mary Fiance Director, Public Relations and Communications, MDA (646) 992-2908

Marcia Semmes Media Relations, CMTA