# Mitofusin Agonists to Treat Neurodegenerative Disease

> **NIH NIH R42** · MITOCHONDRIA IN MOTION, INC. · 2022 · $968,715

## Abstract

Mitofusin agonists for the treatment of neurodegenerative diseases
Gerald W Dorn II, MD
Mitochondria in Motion, Inc.
Washington University in St Louis School of Medicine
Abstract: A number of rare neurodegenerative diseases are characterized by
mitochondrial fragmentation, dysmotility and dysfunction. Among these are Amyotrophic
Lateral Sclerosis (ALS) and Huntington’s Disease (HD), which cause significant
morbidity and mortality in affected populations and for which there are no available
disease-altering therapies. With Phase I STTR support, Mitochondria in Motion, Inc.
(MiM) has developed the first pharmaceutically acceptable small molecule mitofusin
activators to treat these and other neurodegenerative conditions with underlying
contributory mitochondrial pathology. Mitofusin activation enhances mitochondrial
fitness, metabolism and trafficking within diseased neurons, thereby improving
homeostatic functioning, conferring resistance to injury and promoting neuronal
repair/regrowth. During phase I we hypothesized that intervention with a mitofusin
activator would have beneficial effects on etiologically diverse genetic peripheral
neuropathies with a mitochondrial component. This notion was validated by phase I
studies and MiM is advancing 2 pre-clinical lead mitofusin activators, CPR1-B for
sustained activation in genetically heterogenous diseases like ALS and HD not caused
by mitofusin (MFN) mutations, and MiM-111 for “burst” activation in Charcot-Marie-
Tooth disease type 2A (CMT2A) that is directly caused by mutations in MFN2. Having
identified CPR1-B as a clinical candidate in non-CMT2A neuropathies like ALS and HD,
our Phase II goals are to initiate non GMP pre-IND studies positioning us for FDA IND
approval (Aim 1) and define optimal CPR1-B dosing levels and schedule in ALS and HD
mouse models (Aim 2). If successful we will fill an unmet healthcare need and build a
commercial enterprise to serve the ~20,000 Americans with ALS and the ~150,000
Americans suffering from or at genetic risk for developing HD, their caregivers and
families. Our deliverable in Phase II will be a mitofusin activator positioned for FDA IND
approval and phase 1 first-in-human trials.

## Key facts

- **NIH application ID:** 10383118
- **Project number:** 2R42NS113642-03
- **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:** $968,715
- **Award type:** 2
- **Project period:** 2022-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10383118

## Citation

> US National Institutes of Health, RePORTER application 10383118, Mitofusin Agonists to Treat Neurodegenerative Disease (2R42NS113642-03). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10383118. Licensed CC0.

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