# Muscle building supplement HMB for remyelination

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $65,428

## Abstract

Pathologically, multiple sclerosis (MS) can be identified by the presence of diffuse, discrete
demyelinated areas, called plaques. Demyelination is a major feature of MS and therefore, an
approach to the management of MS involves an increase in remyelination of axons, resulting in
clinical improvement. Peroxisome proliferator-activated receptor β or δ (PPARβ) being highly
expressed in the CNS participates in many brain functions including myelination. Being a
nuclear hormone receptor, PPARβ needs ligand(s) for its activation and nuclear translocation.
Therefore, identification of new nontoxic ligand of PPARβ would be very important for
promoting remyelination. The β-hydroxy β-methylbutyrate (HMB) is available in local GNC
stores as a muscle-building supplement in human. It is a physiological molecule that is produced
in human through the metabolism of L-leucine. HMB is known to increase exercise-induced
gains in muscle size and muscle strength and improve exercise performance. Our preliminary
results show that HMB may bind and activate PPARβ and stimulate the maturation of
oligodendroglial progenitor cells (OPCs) to oligodendrocytes (OL), myelin-producing cells in
the CNS. Therefore, here, we will test an exciting hypothesis that HMB binds to the ligand-
binding domain of PPARβ and that HMB and its precursor L-leucine promote maturation of
OPCs and stimulate remyelination in animal models (cuprizone and experimental allergic
encephalomyelitis) of CNS demyelination via PPARβ.
Administrative supplement: Alzheimer’s disease (AD) is the most common neurodegenerative
disorder in humans and despite intense investigations, no effective therapy is available to halt the
progression of AD. Interestingly, our preliminary results show marked demyelination in the
hippocampus and cortex of postmortem AD brains as compared to age-matched control brains
with no cognitive impairment. Similarly, we have seen demyelination in the hippocampus and
cortex of 5XFAD mice, but not age-matched non-transgenic mice. Since the muscle building
supplement HMB activates PPARβ, increases myelin-specific genes and stimulates the
maturation of OPC to OL, here, in response to NOT-AG-20-034 entitled “Notice of Special
Interest: Alzheimer’s-focused administrative supplements for NIH grants that are not focused on
Alzheimer’s disease”, we have planned to test an exciting hypothesis that oral administration of
HMB and its precursor Leu stimulates remyelination and improves cognitive functions in
5XFAD mouse model of AD via PPARβ. A positive outcome of this administrative supplement
will indicate whether demyelination/remyelination is a therapeutic target in AD, enhance the
possibility of promoting remyelination and improving cognitive functions in AD patients with
muscle-building supplement HMB and a simple non-toxic amino acid L-leucine as primary or
adjunct therapy.

## Key facts

- **NIH application ID:** 10281373
- **Project number:** 3R01AT010980-01S1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** KALIPADA PAHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,428
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10281373

## Citation

> US National Institutes of Health, RePORTER application 10281373, Muscle building supplement HMB for remyelination (3R01AT010980-01S1). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10281373. Licensed CC0.

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