# Phase II trial of GM-CSF/sargramostim in Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $1,340,244

## Abstract

PROJECT ABSTRACT
Alzheimer’s disease (AD) treatments designed to target the amyloid-beta peptide have shown encouraging
results in transgenic animal models but less encouraging results in human trials, which have also been plagued
with serious adverse events (SAEs), including amyloid-related imaging abnormalities (ARIAs). Our proposed
innovative therapeutic approach is based on epidemiological evidence that patients with the inflammatory
disease rheumatoid arthritis (RA) have a reduced risk of developing AD, unrelated to their use of non-steroidal
anti-inflammatory drugs (NSAIDs). We identified the innate immune system stimulant Granulocyte-Macrophage
Colony-Stimulating Factor (GM-CSF) as a hematopoietic factor upregulated in RA, which we found reduced
brain amyloidosis and reversed cognitive impairment in transgenic AD mice. Other studies have shown GM-CSF
to be neuroprotective, anti-apoptotic, and neurogenic in several models of neurological diseases and injuries.
We also found that recombinant human GM-CSF(sargramostim/Leukine) treatment is associated with cognitive
improvements in leukemia patients after bone marrow chemo-ablation and hematopoietic cell transplant therapy.
Notably, sargramostim is an FDA-approved drug for increasing the production and differentiation of white blood
cells with an excellent safety record over 30 years. Most importantly, we recently completed a Phase I/II safety
and efficacy trial (NCT01409915) in which mild-to-moderate AD participants were treated with sargramostim
(250 mcg/m2/day SC) or placebo five days/week for three weeks (20:20 participants per group) with neurological,
neuropsychological, neuroimaging, and blood biomarker assessments. Sargramostim treatment was safe
(Primary Endpoint) with no drug-related SAEs and no ARIAs. Furthermore, the Mini-Mental State Exam (MMSE)
showed cognitive improvement in the sargramostim group at the end of treatment (EOT) compared to baseline
(p=0.0074) and in the sargramostim group compared to the placebo group at the EOT (p=0.037) and at 45 days
after the EOT (p=0.0281). Other assessments showed no treatment benefits, but there was a trend negative
correlation between changes in MMSE versus amyloid-PET. We now propose to carry out a randomized, double-
blind, placebo-controlled trial in 42 mild-to-moderate AD participants, 28 of whom will receive sargramostim (250
mcg/m2/day SC) and 14 of whom will receive placebo, five days/week for 24 weeks with a 45-day follow-up visit.
We have received both an IND exemption (134291) and IRB approval (17-0215) but will submit improved
versions in the coming months. Our Specific Aims are: 1) Assess the long-term safety and tolerability of
sargramostim in mild-to-moderate AD participants (Primary Endpoint). 2) Assess the effects of sargramostim
treatment on cognition and activities of daily living in mild-to-moderate AD participants (Secondary and
Exploratory Endpoints). 3) Assess changes in biomarkers associated with sargramostim treatm...

## Key facts

- **NIH application ID:** 10143841
- **Project number:** 1R01AG071151-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Huntington Potter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,340,244
- **Award type:** 1
- **Project period:** 2021-02-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143841

## Citation

> US National Institutes of Health, RePORTER application 10143841, Phase II trial of GM-CSF/sargramostim in Alzheimer's Disease (1R01AG071151-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143841. Licensed CC0.

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