CMT Drug Development Process and Therapy Pipeline

Therapies Under Development in Industry

Therapy Pipeline

CMT Subtype: 1A

In CMT1A, the peripheral myelin protein 22 (PMP22) gene is duplicated leading to the breakdown of the myelin that surrounds peripheral nerves. This causes nerve dysfunction and degeneration. PXT3003 is an orally administered combination of three different chemicals- naltrexone, baclofen, sorbitol- that each act through a different mechanism to lower the levels of PMP22.

CMT Subtype: 1A

MD1003, a form of the B vitamin biotin, targets the enzymes involved in energy production and the synthesis of fatty acids essential for myelin in peripheral nerves. In CMT1A, the myelin sheath in peripheral nerves is degraded leading to nerve dysfunction. MD1003 would be expected to increase myelin production and help nerves function better.

CMT Subtype: 1A

In CMTA 1A Schwann cells are aberrant in their handling of calcium. MP-188 acts to block a protein contributing to elevated levels of intercellular calcium thereby reverting CMT1A Schwann cell function back to that seen in normal cells.

CMT Subtype: 1A & 1B

IFB-088 (also called Sephin1) is an orally active drug that modulates a normal stress response in cells called the unfolded protein response (UPR) which is triggered by abnormal proteins. IFB-088 helps cells to better process the abnormal proteins found in some forms of CMT.

CMT Type 2

Transport of molecules along the length of the nerve axon is critical for maintaining the health of axons. However, axonal transport is disrupted in some forms of CMT leading to death of axons. Inhibitors of histone deacetylase 6 (HDAC6) such as CKD-510 act to improve the internal structure of axons and protect against neuronal damage.

CMT Subtype: 2A

Mitofusin helps to maintain the normal function of mitochondria which generate energy for cells but its function is altered by the mutations found in the mitofusin 2 (MFN2) gene in CMT2A. Mitochondria in Motion, in collaboration with Washington University, is developing novel activators of mitofusin 2 to counteract the effects of these mutations and restore normal energy production for nerves.

CMT Subtype: 1A

In CMT1A, the PMP22 gene is duplicated leading to increased levels of PMP22 and subsequent breakdown of the myelin that surrounds peripheral nerves. This causes nerve dysfunction and degeneration. Activation of the GABAB receptor leads to lower levels of PMP22.

CMT Subtype: 1A

In CMT1A the myelin around peripheral nerves is damaged causing nerve dysfunction and degeneration. CLZ-2002 is a type of cell therapy wherein Schwann cell-like cells are injected locally near specific nerves to help with remyelination of the nerve.

CMT Subtype: 2

Mitochondria provide critical energy for the normal functioning of nerves and other cells. Dysfunctional mitochondria are commonly observed in various diseases including CMT. SBT-259 is designed to restore normal energy production for nerves.

CMT Subtype: 2D & 2F

Transport of molecules along the length of the nerve axon is critical for maintaining the viability of axons. However, axonal transport is disrupted in some forms of CMT leading to death of axons. Ricolinostat inhibits histone deacetylase 6 (HDAC6) which improves the internal structure of axons and protects against neuronal damage.

CMT Type 2

Transport of molecules along the length of the nerve axon is critical for maintaining the viability of axons. However, axonal transport is disrupted in some forms of CMT leading to death of axons. Inhibitors of histone deacetylase 6 (HDAC6) act to improve the internal structure of axons and protect against neuronal damage.

CMT Subtype: 1A

Neurotrophin 3 (NFT3) is a growth factor that improves nerve regeneration and myelination. In this form of gene therapy, NFT3 is delivered by local injection into muscles using a viral vector.

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AcuraStem

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Toolgen

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DTx Pharma

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Shift Pharma

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Today, available treatments for CMT are designed to help people effectively manage disease symptoms. Drugs may be used to lessen pain, and orthopedic surgery to correct joint deformities. Physical and occupational therapy often incorporate strength training, muscle and ligament stretching and exercise to help with muscle weakness and pain. In addition, a range of medical devices including braces, walkers and wheelchairs are used to help maintain mobility, assisted ventilation can help with breathing issues and hearing aids help compensate for hearing loss.

However, with the identification over the past several decades of more than 100 different gene mutations underlying the various forms of CMT, scientists now have a broad range of targets at which to aim therapies that can modify the course of the disease.

CMTRF is working hard today to make good on our promise to deliver safe and effective treatments to people living with all forms of CMT. Our expectation is that the treatments of tomorrow will do more than manage symptoms. Tomorrow’s treatments, under development and testing now, will aim to modify the course of the disease whether by targeting a particular function, or changing a person’s genetic makeup.

Learn more about current clinical trials

The imperative research for the development of CMT treatments is dependent on the funding from organizations like us.

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