Joint Research Grant From MDA, CMTRF Will Focus on CMT4B1

Alessandra Bolino, Ph.D., in Italy, will receive $263,450 to study abnormal myelin structure

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by Andrea Lobo |

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An arrow points from a stack of money to a laboratory test tube.

The Muscular Dystrophy Association (MDA) and the Charcot-Marie-Tooth Research Foundation (CMTRF) have awarded a joint research grant that will examine cellular changes in Charcot-Marie-Tooth (CMT) disease with aberrant myelin.

The research team led by Alessandra Bolino, Ph.D., at San Raffaele Hospital, Italy received a $263,450 grant for three years to investigate the modulation of cellular mechanisms related to abnormal myelin structure as a potential therapy for CMT. Myelin is a fat-rich layer that insulates nerve fibers and aids signal transmission.

“We at the Muscular Dystrophy Association welcome this opportunity to join with CMTRF to support this important research,” Sharon Hesterlee, PhD, chief research officer at the Muscular Dystrophy Association, said in a press release. “Collaborating with like-minded organizations to fund research that may lead to increasing advancements in treatments and cures for Charcot-Marie-Tooth disease will increase our efficiency and help accelerate MDA’s overall mission to improve the lives of neuromuscular disease patients.”

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CMT affects the peripheral nervous system, the network of nerves that control movement and sensations in the limbs. Progressive muscle wasting  and weakness are hallmark symptoms.

The project will focus on CMT type 4B1, a severe form of the disease with early onset. In this rare type, patients typically have muscle weakness starting in the legs and sensory loss, frequently with foot deformities.

CMT4B1 is caused by mutations in the MTMR2 gene, which codes for a protein called myotubularin-related protein 2. MTMR2 mutations lead to a molecule known as PI(3,5)P2 accumulating, causing abnormal myelin structures, or outfoldings, to form, which impair nerve cell function and lead to their death. Myelin outfoldings are a feature of CMT4B2, CMT4B3, CMT4C, and CMT4H, too.

Bolino’s research team previously showed the loss of MTMR2 protein in Schwann cells, which form the myelin sheath in peripheral nerves, causes CMT4B1. The team also identified a novel mechanism by which MTMR2 coordinates cellular processes in myelin-forming cells.

In this new project, the researchers will further explore this mechanism and test whether genetic and pharmacological modulation of related biological pathways can effectively treat CMT4B1.

“The CMT Research Foundation is pleased to partner with the Muscular Dystrophy Association on Dr. Bolino’s CMT4B1 project,” said Cleary Simpson, CEO of CMTRF. “CMTRF is ready to form alliances with organizations that can get us closer to treatments or a cure for CMT.”

In 2021, Bolino teamed with CMTRF and AcuraStem to test if inhibiting an enzyme involved in producing PI(3,5)P2 prevents CMT4B1. The researchers showed that one such inhibitor — apilimod — prevented myelin outfolding formation.