1. Rarebase: Repurposing Drugs Across Multiple CMT Types

In partnership with Rarebase, HNF is leading the first research initiative to tackle multiple types of CMT in a single project. Rarebase is a public benefit biotech company focused on accelerating therapy development for rare diseases through its tech-enabled drug discovery platform called Function.

Rarebase will screen a compound library of thousands of FDA-approved and novel drugs, targeting 10 CMT-related mutations:

  • CMT1A and HNPP (PMP22 duplication and deletion)
  • CMT2A (MFN2, and MFN2 with optic atrophy)
  • CMT6 / Leigh’s Syndrome (C12orf65)
  • CNTNAP1
  • CMT4A and CMT2K (GDAP1)
  • SORD Deficiency
  • CMT4J
  • MTMR2
  • PRX
  • OPA1

Funding goal: $150,000. HNF aims to develop additional human-derived cellular models for testing these mutations. To learn more and support research for your subtype of CMT, please contact us.

2. Novel Drug for Multiple CMT Types: HDAC6 Inhibitors

HNF was the first patient advocacy group to fund research into how HDAC6 inhibition (a class of drugs that modifies gene expression by targeting a specific enzyme) affects CMT2A, testing this drug class in animal models including zebrafish and mice.

Since 2014, HNF has invested $425,000 in HDAC6 inhibitor research. The drug is currently being optimized for human trials and advancing toward a pre-IND (Investigational New Drug application) stage.

This work involves an undisclosed biotech company along with researchers at a New Zealand university, the Burke Institute, and the University of Sheffield.

Funding goal: $250,000. HNF aims to test HDAC6 inhibitors in cellular and animal models for additional CMT subtypes, including CMT1A, CMT4A, CMT2K, and CMT6. To learn more and support research for your subtype, please contact us.

3. Autosomal Dominant Optic Atrophy (ADOA) and the OPA1 Gene

In partnership with Fondazione per la Ricerca Biomedica Avanzata Onlus and the Veneto Institute of Molecular Medicine (V.I.M.M.), HNF was awarded a grant to accelerate the screening of FDA-approved drugs to identify small molecules that counteract the loss of mitochondria in the axons of Retinal Ganglion Cells (RGCs) in ADOA.

Autosomal dominant optic atrophy (ADOA)-plus syndrome is a rare inherited neuropathy affecting the OPA1 gene. It can involve vision loss, weakness in the muscles that control eye movement (progressive external ophthalmoplegia), difficulty with balance and coordination (ataxia), hearing loss, nerve damage affecting movement and sensation (motor and sensory neuropathy), and muscle weakness (myopathy). Rates and severity of these features vary by individual.

As of this announcement in April 2022, HNF expected to have an initial progress report in mid-2022.