# Muscle building supplement HMB for remyelination

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2022 · $392,500

## 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: One of the pathologic hallmarks of Alzheimer’s disease (AD) is the
presence of neurofibrillary tangles containing aggregated tau. Effective reduction of aggregated
tau from the brain parenchyma is expected to reduce the disease process of AD, progressive
supranuclear palsy (PSP), frontotemporal dementia (FTD), and other tauopathies. Despite intense
investigations, no effective therapy is available to reduce tauopathy. Since microglial activation
plays an important role in different neurodegenerative disorders including tauopathy, we
examined the effect of muscle-building supplement HMB on microglial activation and found that
HMB is capable of inhibiting tau fibril-mediated activation of microglia in culture as well as
suppressing glial inflammation in vivo in the hippocampus of P301S Tau or PS19 mouse model
of AD. Therefore, this administrative supplement in response to NOT-AG-21-018 has been
devoted to test an exciting hypothesis that oral administration of HMB and its precursor L-
leucine inhibits microglial inflammation to lower tauopathy and improve cognitive functions in
PS19 mouse model of AD. A positive outcome of this administrative supplement will enhance
the possibility of inhibiting microglial activation, lowering tauopathy and improving cognitive
functions in patients with AD, PSP, FTD, and other tauopathies with muscle-building
supplement HMB and a simple non-toxic amino acid L-leucine as primary or adjunct therapy.

## Key facts

- **NIH application ID:** 10499062
- **Project number:** 3R01AT010980-03S1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** KALIPADA PAHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,500
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499062

## Citation

> US National Institutes of Health, RePORTER application 10499062, Muscle building supplement HMB for remyelination (3R01AT010980-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499062. Licensed CC0.

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