# GM-CSF/sargramostim treatment to improve cognition in Down syndrome

> **NIH NIH R61** · UNIVERSITY OF COLORADO DENVER · 2021 · $345,544

## Abstract

PROJECT SUMMARY/ABSTRACT
People with Down syndrome (DS) exhibit significant hypoplasia of the frontal lobe, hippocampus, and cerebellum
and mild to severe intellectual disability, which challenges their ability to function independently. Any
enhancement of their cognitive ability would greatly improve their quality of life and activities of daily living, but
currently there are no therapeutics available for enhancing cognitive function in people with DS. This proposal
aims to design and complete a clinical trial in adults with DS using recombinant human granulocyte-macrophage
colony-stimulating factor (GM-CSF/sargramostim), an FDA-approved drug for increasing the production and
differentiation of various white blood cells with almost 30 years of excellent safety history in numerous patient
populations. In a previous retrospective study, we found that sargramostim treatment is associated with cognitive
improvements in leukemia patients after bone marrow chemoablation and hematopoietic cell transplantation. In
a recently concluded Phase II clinical trial (NCT01409915), we found that three weeks of sargramostim treatment
was safe and well tolerated in mild-to-moderate Alzheimer’s disease (AD) participants and was associated with
improvement in the MMSE, reduced biomarkers of neurodegeneration (Tau and UCH-L1), but no evidence of
reduced amyloid. Furthermore, we have found that treatment with murine GM-CSF improves cognition and
ameliorates astrogliosis in a mouse model of DS (which has no AD pathology), that it rapidly reverses cognitive
impairment and removes some cerebral amyloid pathology in mouse models of AD, and that it improves age-
related cognitive decline in aged wild-type mice. Numerous other studies have shown that GM-CSF is
neuroprotective, anti-apoptotic, neurogenic, and beneficial in several neurological diseases and injuries, for
example, in a clinical trial with Parkinson’s disease subjects and in animal models of stroke, spinal cord injury,
and traumatic brain injury. Specifically, this proposal is designed to investigate whether treatment with
sargramostim at the FDA-recommended dose is safe and tolerable in adults with DS, whether it can improve
measures of cognitive function, quality of life, and activities of daily living, and whether it can reduce the Tau and
UCH-L1 biomarkers in the blood that we have shown to evidence neuroinflammation and neurodegeneration in
people with DS and to be reduced in AD patients by GM-CSF treatment.

## Key facts

- **NIH application ID:** 10304446
- **Project number:** 1R61AG074859-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Huntington Potter
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,544
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10304446

## Citation

> US National Institutes of Health, RePORTER application 10304446, GM-CSF/sargramostim treatment to improve cognition in Down syndrome (1R61AG074859-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10304446. Licensed CC0.

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