CMT Research Foundation, Samsara Team Up on New CMT1A Treatment

Partners to focus on compounds to restore cell recycling

José Lopes, PhD avatar

by José Lopes, PhD |

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New partners shaking hands on development deal.

Note: This story was updated Oct. 21, 2022, to correct that the compounds being developed aim to restore autophagy in Schwann cells, not muscle cells.

The CMT Research Foundation (CMTRF) has teamed up with Samsara Therapeutics to accelerate the development of compounds to restore autophagy — the process by which cells degrade or recycle components that are damaged or no longer needed — in the Schwann cells surrounding nerves of people with Charcot–Marie–Tooth disease type 1A (CMT1A).

Representing CMTRF’s largest investment to date, the partnership aims to support the clinical development of Samsara’s pipeline of autophagy-targeting compounds.

The goal is to more quickly initiate clinical trials to test these compounds for the treatment of CMT1A patients.

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“To our knowledge, Samsara Therapeutics is the only company so far pursuing an approach that targets autophagy-induced restoration of neuromuscular function in CMT1A,” Cleary Simpson, CEO of the CMTRF, said in a press release.

“This pipeline asset has the potential to be a game-changing therapeutic for CMT patients,” Simpson said.

Added Keith Fargo, PhD, chief scientific officer at CMTRF: “This project is designed to further optimize these compounds, then scale up manufacturing of the candidate, and subject it to profiling studies to determine if the potential therapeutic has favorable drug properties for first-in-human dosing in clinical trials.”

CMT1A, the most common CMT subtype, is mostly caused by a duplication of the PMP22 gene. This leads to an overproduction of the PMP22 protein, which impairs its incorporation into the myelin sheath (a protective sheath of nerve fibers), produced by Schwann cells outside the brain and spinal cord. This leads to myelin loss, nerve cell damage, and disability.

While the mechanism of disease in CMT1A is not completely understood, scientists hypothesize that the extra PMP22 protein clumps to form toxic aggregates or clumps that disrupt normal cellular function.

“There is compelling evidence from human genetics that many diseases are driven by autophagy dysfunction. Samsara’s mission is to discover new mechanisms which can restore autophagy and deploy new drugs targeting these mechanisms for the treatment of genetically defined diseases like CMT1A,” said Peter Hamley, PhD, Samsara’s chief scientific officer.

According to the company, in studies with a mouse model of CMT1A, Samsara’s approach was able to stimulate autophagy in nerve fibers and Schwann cells. This restored neuromuscular function in a dose-dependent manner, as seen in the sciatic nerve, which travels from the lower back down into each leg.

“This investment by the CMT Research Foundation and our close working relationship with their network of leaders in the field shows great promise,” said Hamley.

“We are gratified by the trust placed in our team and are confident that we will make significant progress towards developing a first disease-modifying therapeutic for patients living with CMT1A,” he added.