# Adipose-derived stem cell-conditioned medium therapy in a mouse model of ALS

> **NIH VA IK2** · RLR VA MEDICAL CENTER · 2021 · —

## Abstract

Amyotrophic lateral sclerosis (ALS) is a prevalent progressive neurodegenerative disease involving
the loss of functional neuromuscular junctions (NMJ) and motor neurons (MN), and subsequent
paralysis. No effective cures for ALS exist and current therapies only marginally impact disease
course. This is because at the time of diagnosis, the disease has typically progressed into the final
stages which impedes effective treatment. Therefore, treatment of ALS with novel therapies is an
unmet need. Since veterans of the Persian Gulf War are twice as likely to develop ALS, discovering
successful therapies is especially significant to our veteran population. Adipose-derived
stem/stromal cells (ASC) have been shown to repair and rescue tissues from ischemia and other
pathological conditions due to their beneficial secretions including anti-apoptotic, anti-inflammatory,
and pro-angiogenic growth factors and cytokines. Recent studies have demonstrated the therapeutic
value of conditioned medium isolated from ASC cultures (ASC-CM), and Phase I clinical trials
utilizing ASC-CM to treat acute lung injury and specific cardiovascular pathologies are also ongoing.
In this context, we have identified a B6SJL hybrid mSOD1G93A mouse model of ALS in which disease
progression is similar to that observed in ALS patients. Evidence shows ASC-CM administration in
this ALS mouse model after symptom onset improves lumbar spinal cord MN survival and prolongs
lifespan. Moreover, early ASC-CM treatment (at disease onset) preserves intact NMJ. Therefore,
early ALS treatment using ASC-CM may simultaneously target peripheral and central components
of ALS. Using the mSOD1G93A ALS mouse model, we will also administer local muscular injection of
a novel bioengineered ASC-CM-embedded polyethylene glycol (PEG) hydrogel that allows slow
release of growth/protective factors at the site of neuromuscular disconnection to investigate the
specific site(s) of ASC-CM action. We will also assess the overall efficacy for clinical translation of
ASC-CM through optimized amelioration of disease progression. Three specific Aims have been
designed to elaborate on this areas of investigation.
Aim 1: Determine ASC-CM dose response on early NMJ loss, and assess neuromuscular and
immune responses to long-term ASC-CM therapy in mSOD1G93A mice. A) First, an experiment will
be performed to determine the optimal therapeutic dose of ASC-CM required to preserve intact NMJs. B)
The optimal dose of ASC-CM from (A) will be administered from PD35-PD47 and NMJs and MN will be
quantified weekly from PD56-91 and compared with C) the optimal dose of ASC-CM administered from
PD35-continuously.
Aim 2: Determine the therapeutic efficacy of early long-term continuous ASC-CM administration
in mSOD1G93A mice. Using the optimal ASC-CM dose established in Aim 1, symptom onset, disease
progression rate, and lifespan will be assessed and histologic analyses performed. To assess symptom
onset and progression an array of funct...

## Key facts

- **NIH application ID:** 10112112
- **Project number:** 5IK2RX002688-03
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** Chandler Walker
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112112

## Citation

> US National Institutes of Health, RePORTER application 10112112, Adipose-derived stem cell-conditioned medium therapy in a mouse model of ALS (5IK2RX002688-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10112112. Licensed CC0.

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