CMT is not rare to me.

Celebrate Rare Disease Day by taking action to deliver treatments and cures for CMT.

Charcot-Marie-Tooth (CMT) is a family of genetic peripheral nerve diseases with over 100 known genetic causes. CMT can either be a primarily axonal disease or a demyelinating disease. Eventually, CMT affects both the myelin and the axons of the peripheral nervous system. Onset can be at birth or later in life and is characterized by degeneration of the nerves and loss of sensation in the feet, hands, legs and arms. It is a progressive disease and can lead to severe disability or even death. Nearly 3 million people of every age, race and ethnicity are living with CMT. Currently, there are no treatments or cures that target the disease.

CMT research funding will be targeted to the key focus areas below. However, the program is open to transformative projects that may fall outside the scope of these areas.  Please inquire further if your idea does not fit the focus area.

CMT Research Foundation’s Primary Focus Areas

Pharmacodynamic Barriers: Research the barriers to therapeutic efficacy in CMT:

  • Understand and overcome limited drug exposure to Schwann cells (e.g. Examine the mechanisms that prevent drugs (ASO, small molecules, biologics, etc.) from achieving an effect.
  • Explore how the blood neural barrier (BNB) prevents drug treatments from reaching Schwann cells and axons. Examine the barriers in Schwann cells that prevent cellular uptake of therapeutics. Areas of support may include the development of robust cellular models to test therapeutics routinely for their ability to cross the BNB. These models could be similar to those developed that have been employed to model the blood-brain barrier (MDCK-PGP etc.). These models should be able to be industrialized and implemented in pharmaceutical laboratories to optimize therapeutics for BNB penetration.

CMT Molecular Drug Targets: Therapeutic drug targets to prevent axonal degeneration. The CMTRF’s goal is to understand the molecular basis for axon degeneration in CMT, with the specific aim of identifying druggable targets that are well-positioned for therapeutic discovery. Projects may be focused on establishing validated in vitro cellular models specific to CMT pathology that can demonstrate the involvement of molecular targets in CMT axon degeneration or that can be utilized for phenotypic drug/target discovery efforts.

Pathophysiologically Relevant Animal Models:  The goal of this focus area is to create new animal models that more fully represent the human forms of CMT. The aim is to create novel transgenic models that support therapeutic drug discovery and development. These animal models would be made widely available to the research community.

Stem Cell-Derived Cellular Models of CMT:  Suitable for high-throughput screening (HTS) testing – axonal and myelinating models. Although human neurons and Schwann cells can be generated from iPSCs in vitro, there has been limited success creating faithful models of completely myelinated neurons (in the case of demyelinating neuropathies) and phenotypic axons (in the case of axonal neuropathies) to test therapeutics and study CMT. The focus of this program is aimed at enhancing the generation of myelinated human axons in vitro. Importantly, the models should be able to reveal differences between CMT and unaffected patients’ cells derived from iPSCs. The primary objective is an HTS-suitable assay.