2 CMT Research Projects Among 25 MDA Grants Totaling More Than $6.6M

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by Joana Carvalho, PhD |

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The Muscular Dystrophy Association (MDA) has awarded 25 research grants totaling more than $6.6 million to scientists working on different neuromuscular diseases (NMDs), including Charcot-Marie-Tooth disease (CMT).

This round of grant funding builds on the more than $1 billion the MDA has already invested to promote the discovery of new therapies and potential cures for these disorders since its foundation and the organization’s continued commitment to scientific innovation.

“MDA’s latest group of awards aims to support the most promising research in a variety of neuromuscular diseases,” Lianna Orlando, PhD, MDA’s former interim head of research, said in a press release. “Each funding award will address a key challenge or gap in knowledge and build upon the advances that have taken place in the last several years.”

The 25 funded projects all share a common goal: to advance research and promote the development of new therapies for a particular NMD. Other than CMT, the projects involve work on a variety of diseases including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, spinal muscular atrophy, and Friedreich’s ataxia.

Because the MDA is also committed to supporting the work of scientists taking the first steps in their careers, five of these research grants have been given to researchers who are now in the process of becoming independent investigators. The other 20 have been granted to researchers who have already established themselves as independent scientists.

Two of the grants have been awarded to two scientists working on projects in CMT.

One of the awardees, Charlotte Sumner, MD, professor of neurology and neuroscience at Johns Hopkins University School of Medicine in Baltimore, received $300,000 over a three-year period for a project titled, “A key role for TRPV4 in neurodegeneration via control of the blood-nerve barrier.”

Summer and her team will focus their efforts on investigating how genetic mutations in the transient receptor potential vanilloid 4 (TRPV4) gene may lead to the development of CMT type 2C (CMT2C) and distal SMA.

More specifically, they are planning to investigate the effects TRPV4 may have on how endothelial cells — the cells that make up the lining of blood vessels — regulate the blood-nerve barrier, which protects the brain from harmful substances that may be found in the blood circulating in the rest of the body.

“Defining the mechanisms by which TRPV4 mutations cause neuropathy [nerve disease] is important because TRPV4 protein is a readily druggable therapeutic target — it is expressed at the plasma membrane and small molecules acting on it already exist,” the investigators wrote in their project proposal.

The second awardee, Gerald W. Dorn II, MD, professor of medicine and director of the Center for Pharmacogenomics at Washington University School of Medicine in St. Louis and president of Mitochondria in Motion, received two-year funding totaling $267,942 for a project titled, “Mitofusin agonists to treat Charcot-Marie-Tooth disease.”

Dorn and his team will focus on investigating the therapeutic effects of a compound they had previously discovered for the treatment of CMT type 2A (CMT2A).

CMT2A is caused by mutations in the MFN gene, which provides instructions to make a protein called mitofusin 2. The compound Dorn and his colleagues discovered mimics the function of mitofusin 2, which does not work properly in patients with CMT2A.

In cellular models of CMT2A, the compound successfully reverted some CMT2A abnormalities. Now Dorn is planning to use the new funding to continue studying the effects of the compound in a humanized mouse model of CMT2A that will hopefully move the research closer to human clinical testing.

“There is currently no disease-modifying treatment for CMT2A; mitofusin agonists may be the first. This is an orphan disease with a clear unmet need,” Dorn said.

For a complete list of the 25 research grants, visit the MDA’s website.