# Reversing Skeletal Muscle Myopathy by Hydrogen Sulfide

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2021 · $328,636

## Abstract

Children born with severe homocystinuria due to homozygous cystathionine beta synthase deficiency (CBS-/-)
exhibit poor body weights, skeletal muscle myopathy and die in teenage. Although mice with homozygous CBS
mutation die shortly after birth, the heterozygous CBS-/+ survives. Our preliminary data suggests that
enzymes, CBS and cystathionine gamma-lyase (CSE) that irreversibly remove homocysteine (Hcy) by
converting to hydrogen sulfide (H2S), are decreased in skeletal muscle. Although lowering of Hcy levels and
generation of H2S is beneficial, the mechanism by which HHcy causes of skeletal muscle wasting and frailty is
unknown. The long-term goal of this project is to understand the mechanism of muscle wasting in HHcy and
evaluate the potential beneficial effects of H2S signaling in reversing skeletal muscle wasting and myopathy.
The central hypothesis of this proposal is that HHcy causes skeletal muscle deterioration by
compromising vasculogenesis, by enhancing muscle atrophy and by limiting skeletal muscle
regeneration and H2S reverses these changes. We will test this hypothesis by following three specific aims:
Specific Aim #1: To determine whether the HHcy inhibits muscle specific AKT, HIF-1, and AMPK
signaling and impairs vasculogenesis and H2S reverses impaired vasculogenesis.
Specific Aim #2: To determine whether the HHcy attenuates PGC-1 signaling and instigates atrogene
expression and causes muscular atrophy and H2S mitigates muscle atrophy.
Specific Aim #3: To determine whether the HHcy enhances TGF-1 signaling and myostatin levels,
thereby suppresses muscle regeneration and H2S ameliorates these changes.

## Key facts

- **NIH application ID:** 10089145
- **Project number:** 5R01AR071789-03
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Suresh C. Tyagi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,636
- **Award type:** 5
- **Project period:** 2018-09-21 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089145

## Citation

> US National Institutes of Health, RePORTER application 10089145, Reversing Skeletal Muscle Myopathy by Hydrogen Sulfide (5R01AR071789-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089145. Licensed CC0.

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