The Charcot-Marie-Tooth Association (CMTA) has awarded approximately $1 million in grants to scientists worldwide investigating treatments and a cure for the disease of the peripheral muscle-controlling nerves.
The grants bring to more than 50 the number of Strategy to Accelerate Research (STAR) projects the association is funding, according to a news release. The most recent round covers CMT 1, 2 and 4 treatment, from understanding disease mechanisms to uncovering new therapeutic targets.
Along with the Muscular Dystrophy Association, the CMTA awarded Kleopas A. Kleopa, MD, of the Cyprus Institute of Neurology and Genetics, $276,000 for a gene therapy project that could affect all CMT1 patients. The project will test the impediment qualities of adeno-associated virus delivery of the GJB1 gene in CMT1X.
The disorder is thought to be caused by mutations in the GJB1 gene, located on the X chromosome, which encodes for a protein called connexin-32. The abnormal protein is thought to impair the formation of channels and subsequent myelin layer, causing CMT.
For CMT 1B, Maurizio D’Antonio, PhD, of Italy’s Scientific Institute San Raffaele, got $104,000 to confirm whether compounds that activate Ire1a-mediated Xbp1 splicing can assist myelination in dorsal-root-ganglia (DRG) cultures. He will also research how the ATF6a gene affects neuropathy (nerve damage), a common CMT symptom. He hopes that targeting stress-responsive signaling pathways will offer a way to lessen imbalances in proteostasis, the process that regulates protein within cells.
Kleopa also received $120,000 to create a gene therapy treatment for CMT4C, a neuropathy caused by autosomal recessive mutations in the SH3TC2 gene. He has already demonstrated in a CMT4C model that a gene delivered by intrathecal injection (into the spinal canal) offers some benefit. Kleopa will test the approach in a mouse model of the disease at early and late neuropathy stages. The CMTA is requesting patient participation. For more information, email [email protected]
The University of Pennsylvania’s Steven Scherer, MD, got $120,000 to test whether axonal degeneration in the CMT1X mouse model can be improved by crossing it with the SARM1-null, known to reduce degenerative compounds. Scherer hopes to determine whether enzyme antagonists can protect against degeneration.
In addition, Michael Shy, MD, lead researcher for the Inherited Neuropathies Consortium (INC), received $206,000 to back INC’s quest to find therapies for those with inherited neuropathies. To date, INC has enrolled some 10,200 patients. Reaching trial readiness is INC’s main goal. Patients can go to the website to learn how to participate in advance of clinical trials.
Elsewhere, physicians Kate Eichinger and David Herrmann of the University of Rochester Medical Center were awarded $109,000 to study the dependability, validity, and responsiveness of wearable sensors in CMT1A patients, including measures of patient strength and balance. The study aims to provide early data necessary for planning clinical trials.
Shy’s lab also got a $50,000 follow-up grant for continued work on biomarkers necessary for measuring progress in trials to determine whether certain biomarkers can be useful in assessing disease statuses in CMT1A, 1B, 1X and 2A.
Affecting 2.8 million individuals worldwide, CMT causes loss of normal function and/or sensation in the lower legs, feet, hands and arms.