Sargramostim Shows Safety and Promise as Potential Alzheimer Treatment


The investigators wrote that the Alzheimer’s Association “Part the Cloud” funded 24-week treatment trial is now warranted after sargramostim showed a safe and tolerable profile.

Huntington Potter, PhD

Huntington Potter, PhD

Data from a phase 2 study presented at the 2020 Alzheimer’s Association International Conference (AAIC) annual meeting, July 26—30, showed that treatment with sargramostim (Leukine; Partner Therapeutics), a recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF), was safe and showed promise as a potential treatment for Alzheimer disease (AD).1

Presented by Huntington Potter, PhD, director, Alzheimer’s and Cognition Center, and professor of neurology, University of Colorado, patients who received the agent had no drug-related serious adverse events (AEs), including no amyloid-related imaging abnormalities (ARIAs) such as micro-hemorrhage or vasogenic edema.

The double-blind phase 2 study included 40 patients with mild-to-moderate AD, half of which received placebo and half who received 250 ug/m2 per day sargramostim by subcutaneous injection 5 days per week for 3 weeks, with follow-up visits at 45 and 90 days post-treatment. At the end of treatment, those in the sargramostim group showed improvements on their mean Mini-Mental State Examination (MMSE) scores relative to baseline (P = .0074). Improvements were also seen in the placebo group by repeated measures mixed model analysis (P = .037).

Potter and colleagues noted that the beneficial impact of treatment with sargramostim on MMSE compared to placebo was still retained in patients at the first follow-up visit, 45 days after the end of treatment (P = .0272). On the other hand, there was a single poorer Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) mean score in the sargramostim group compared to placebo at the first follow-up on Day 45 post-treatment.

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The primary outcome measure was patient tolerability to sargramostim and secondary outcome measures were aimed at assessing the ability to improve cognition in those with AD. Potter et al. noted that data on amyloid and volumetric brain scans from treatment are still being analyzed.

Improvements on MMSE along with showing a safe profile led the investigators to conclude that GM-CSF or sargramostim has promise as a potential treatment for AD and that the Alzheimer’s Association “Part the Cloud” funded 24-week treatment trial is warranted to further understand more about the therapy in this population.

Previous notions of patients with rheumatoid arthritis (RA) having a reduced risk of developing AD led Potter and colleagues to hypothesize that intrinsic innate immune system factors associated with RA may underlie the AD protective effects. Sargramostim was among many tested cytokines upregulated in RA blood and was able to show a reduction of cerebral amyloidosis by greater than 50% and completely reverse the cognitive impairment of transgenic AD in mice models.

Sargramostim was then moved to a retrospective study where it showed improved cognition of leukemia patients following bone marrow chemoablation or hematopoietic cell transplant when paired with G-CSF compared to patients who received G-CSF alone.

The FDA approved the use of sargramostim to increase survival in adult and pediatric patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic syndrome of Acute Radiation Syndrome; [H-ARS]) in March 2018. At the time, it became the third FDA-approved medical countermeasure that is indicated to increase survival in patients exposed to myelosuppressive doses of radiation.2

For more coverage of AAIC 2020, click here.


1. Potter H, Woodcock JH, Boyd T, et al. Double-blind placebo controlled trial of safety and efficacy of GM-CSF/Sargramostim in subjects with mild-to-moderate Alzheimer’s disease. Presented virtually at AAIC 2020, July 26-29. Poster 46497.

2. FDA approves Leukine for acute radiation syndrome. News release. FDA. March 29, 2018. Accessed August 4, 2020.,radiation%20damages%20the%20bone%20marrow.

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