# Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A

> **NIH NIH R42** · MITOCHONDRIA IN MOTION, INC. · 2022 · $901,762

## Abstract

Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A
Gerald W Dorn II, MD
Mitochondria in Motion, Inc.
Washington University in St Louis School of Medicine
Abstract: Charcot-Marie-Tooth (CMT) disease type 2A is an incurable, primarily
pediatric, autosomal dominant neuromuscular degenerative disease caused by
mutations in the mitofusin (MFN) 2 gene. There are currently no disease-altering
treatments. With Phase I STTR support, Mitochondria in Motion, Inc. has
developed the first pharmaceutically acceptable small molecule mitofusin
activator to treat CMT2A and possibly other neurological diseases. In general,
mitofusin activation enhances mitochondrial fitness, metabolism, and trafficking
within neurons, thus improving homeostatic functioning and injury-responses.
Our clinical lead mitofusin activator, trans-MiM111, normalizes mitochondrial
abnormalities in CMT2A patient fibroblasts and reprogrammed neurons in vitro,
and reverses neuromuscular dysfunction in mice expressing a human CMT2A
MFN2 mutant (T105M) in vivo. During STTR Phase I we validated our
hypothesis that activating endogenous, genetically normal MFN2 and MFN1
could reverse dominant inhibition by CMT2A MFN2 mutants of neuronal
mitochondrial fusion and trafficking, thus preventing CMT2A-induced
neuromuscular degeneration. Having identified a pharmaceutically acceptable
clinical candidate, trans-MiM111, our Phase II goals are to define optimal dosing
levels and schedule using our CMT2A mouse (SA#1), and initiate GLP (non-
GMP) pre-IND studies to position us for FDA approval of first-in-human trials. If
we are successful, we will fill an unmet healthcare need and build a commercial
enterprise to serve the ~10,000 Americans with CMT2A and the >200,000
Americans suffering from other neurodegenerative diseases characterized by
mitochondrial degeneration, including CMT type 1, amyotrophic lateral sclerosis,
and Huntington’s disease. Our deliverable for this 2 year Phase II STTR will be a
mitofusin activator positioned for FDA approval and phase I, first in human, trials.

## Key facts

- **NIH application ID:** 10471364
- **Project number:** 5R42NS115184-03
- **Recipient organization:** MITOCHONDRIA IN MOTION, INC.
- **Principal Investigator:** Gerald W. Dorn
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $901,762
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471364

## Citation

> US National Institutes of Health, RePORTER application 10471364, Mitofusin agonists to prevent Charcot-Marie-Tooth disease 2A (5R42NS115184-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10471364. Licensed CC0.

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