# Targeting the fibroblast growth factor binding protein-1 to slow degeneration of neuromuscular junctions

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $326,899

## Abstract

Project Summary/Abstract
The loss of motor function that occurs with aging is closely associated with adverse health
outcomes. In recent years, published findings strongly suggest that malfunction and
degeneration of the neuromuscular junction (NMJ), the synapse formed between α-motor
neurons and skeletal muscle fibers, contributes to age-related motor dysfunction. As the final
output of the somatic motor system, degeneration of the NMJ inevitably results in degeneration
of motor axons and atrophy of muscle fibers, thus affecting voluntary movement. Thus, it is
critical to identify factors that function to maintain and repair the NMJ. Using an R56 grant
provided by NIA, our lab has identified the fibroblast growth factor binding protein 1 (FGFBP1)
as a promising candidate factor secreted by muscle fibers to preserve and restore the integrity
of NMJs during aging. FGFBP1 functions to chaperone FGF ligands from the extracellular
matrix to cognate receptors. In this manner, it enhances FGF signaling. We have found that
while FGFBP1 concentrates at NMJs in young adult mice, it progressively decreases during
normal aging and in SOD1G93A mice, a mouse model for ALS. Using knockout mice, we
observed that FGFBP1 expression is required to slow aging of NMJs and motor deficits during
normal aging. Furthermore, FGFBP1 deletion in mice expressing SOD1G93A, a model for
amyotrophic lateral sclerosis (ALS), accelerates NMJ degeneration, disease progression and
death. These initial discoveries strongly suggest that preventing loss of endogenous of
FGFBP1 during aging may be sufficient to slow degeneration of NMJs, and thus preserve motor
function. To test this hypothesis, we proposed three specific aims that build on each other. In
aim 1, we test the hypothesis that motor deficits in mice deficient for FGFBP1 result from
cellular, molecular, and physiological changes at NMJs. In aim 2, we will seek to identify
molecular mechanisms that inhibit FGFBP1 expression in aging muscles. In aim 3, we will test
the hypothesis that FGFBP1 is sufficient to prevent and reverse age-related changes of NMJs.
These aims are designed to uncover the initial changes that precipitate aging of NMs, the
molecular factors that result in decreased FGFBP1 expression in aging muscle, and the
therapeutic potential of FGFBP1 in preserving NMJs and motor function.

## Key facts

- **NIH application ID:** 9903183
- **Project number:** 5R01AG055545-05
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Gregorio Valdez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,899
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903183

## Citation

> US National Institutes of Health, RePORTER application 9903183, Targeting the fibroblast growth factor binding protein-1 to slow degeneration of neuromuscular junctions (5R01AG055545-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9903183. Licensed CC0.

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