CMT Association Grants $335K to Research Projects that Advance Therapy Development

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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PXT3003 for CMT1A

The Charcot–Marie–Tooth Association (CMTA) has granted $335,000 to two research projects focused on the development of new therapies for Charcot–Marie–Tooth (CMT) disease type 1A, type 1B, and other demyelinating forms of CMT, including type 4.

CMTA has been funding projects for 30 years on research focused on discovering the mechanisms involved in CMT and on developing safe and effective therapies for the 2.8 million living with CMT worldwide.

The association launched its Strategy to Accelerate Research (STAR) initiative in 2008 to bring together scientists, pharmaceutical companies, and patients to create a multidisciplinary collaborative environment that would advance scientific and medical innovation in CMT.

CMTA’s STAR Advisory Board includes 30 leading scientists and clinicians who are responsible for analyzing the quality of ongoing projects and deciding which ones receive monetary support.

A grant totaling $154,000 was awarded to a collaboration project between three leading CMT experts — Kleopas Kleopa, MD, PhD, from The Cyprus Institute of Neurology & Genetics; John Svaren, PhD, from the Waisman Center at the University of Wisconsin-Madison; and Steven Gray, PhD, from the University of Texas Southwestern Medical Center.

Their project will focus on the development of two different types of gene therapies. One therapy is designed to shut down the PMP22 gene, which is overactive in people with CMT1A. The second treatment candidate is designed to replace the defective genes responsible for the different forms of CMT4 and CMT1X.

The scientists will attempt to come up with safe viral vectors to deliver the modified versions of these genes to Schwann cells — specialized cells that produce the fatty substance (myelin) protecting nerve cells — which are defective in CMT.

The team is planning to test the efficacy of four different types of adeno-associated viruses (AAVs), developed by Gray, to determine the one that could better deliver the modified genes to Schwann cells in cases of CMT1A and CMT1X. The researchers will also test the efficacy of two AAVs in a mouse model of CMT1A.

“The proposed experiments will seek to enable a translatable gene therapy approach for CMT1A, CMT1X, and various CMT4 forms. This will also be the first testing of AAV9 virus distribution to Schwann cells in a larger animal model (primate),” the researchers said in their project proposal.

The second grant, which totaled $180,000, was awarded to a collaboration project between Maurizio D’Antonio, PhD, from the IRCCS Ospedale San Raffaele and Ghjuvan Shackleford, PhD, from the Hunter James Kelly Research Institute.

Their project will focus on investigating the mechanisms of disease in a mouse model of late-onset CMT1B (named P0T124M) and discovering new therapeutic strategies to prevent the degeneration of nerve cells and their extensions (required for the proper transmission of nervous signals).

“This project will identify signals and molecules that underlie glial support of axons, and could reveal new unifying therapeutic targets that are common to a large spectrum of neurodegenerative diseases,” the researchers stated.