Name: Sargramostim
Synonyms: GM-CSF Leukine , Leukine®
Therapy Type: Other
Target Type: Inflammation (timeline), Other (timeline), Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Genzyme, Partner Therapeutics, Inc., Sanofi
Approved for: Bone Marrow Stimulation


GM-CSF leukine, aka sargramostim, is a synthetic form of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor. It is a 127-amino-acid glycoprotein produced by recombinant DNA technology in yeast. Sargramostim stimulates the innate immune system. It is FDA-approved for regenerating neutrophils, monocytes, and macrophages after bone marrow transplants, radiation therapy, and in conjunction with treatment for several types of leukemia. Sargramostim is also used for treating neutropenia, a condition of dangerously low white-blood-cell counts. Sargramostim is not to be confused with filgrastim, a recombinant form of the related granulocyte colony-stimulating factor (G-CSF). 

The rationale for evaluating this immune modulator in Alzheimer's disease is that it might increase phagocytosis of pathogenic protein deposits by bone-marrow-derived macrophages or brain-resident microglia, and that it might also stimulate other neuroprotective innate immunity processes. GM-CSF was reported to activate microglia in response to amyloid pathology without also augmenting microglial release of pro-inflammatory cytokines, as is seen in response to other, closely related neurotrophic factors (Murphy et al., 1998). 

In transgenic mouse models of Alzheimer's disease, GM-CSF was reported to reduce amyloid pathology, improve cognition, and increase the number of microglia (Boyd et al., 2010Kiyota et al., 2018). However, contradictory findings exist, as well (Manczak et al, 2009). 

Both GM-CSF and its receptor appear to be expressed in aging human brains, both in controls and in people with Alzheimer's (Ridwan et al., 2012). Analysis of archived neuropsychology data from 19 patients who had received sargramostim as part of their supportive care for bone-marrow transplantation reported a cognitive benefit (Jim et al., 2012). 


In 2011, a Phase 2 randomized study at the University of Colorado, Denver, and the Byrd Alzheimer's Institute of the University of Southern Florida, Tampa, started enrolling 40 patients with mild to moderate Alzheimer's disease to evaluate a three-week course of GM-CSF Leukine (250 microg/m2 per day) or placebo injected under the skin for five days each week. Tolerability was the primary outcome, to be monitored for six months. Various cognitive tests were to be performed for up to six months after treatment as a secondary outcome. This study was set to complete in December 2017. 

At the 2017 AAIC, investigators presented interim data on 32 participants, 13 on drug and 19 on placebo (Aug 2017 conference news). Patients were examined at baseline, at the end of the trial, and 45 and 90 days later, for safety and with cognitive and functional tests. Those in the treatment arm had an average MMSE score of 16.46 at baseline, versus 20.63 for those on placebo, a significant difference; ADL scores were also lower—54.61 for the treatment group and 63.16 for placebo. GM-CSF Leukine seemed well-tolerated, with no serious adverse events reported and no signs of ARIA. Patients on drug scored about 1.5 points higher in MMSE than at baseline; placebo scores stayed unchanged. ADL score rose about 1.5 points in the treatment group at three weeks, but then fell similarly in treatment and placebo arms, respectively. No differences were reported between the two groups at later time points. No significant difference emerged at any time between treatment and placebo arms on the ADAS-Cog, CDR-SB, or MOHS tests.

The trial ended in December 2019, with 40 patients completing treatment and both followup visits. According to results presented at the November 2020 CTAD conference, there were no serious adverse events attributed to drug, and no amyloid-related imaging abnormalities. At the end of treatment, the sargramostim group improved on the MMSE compared to baseline or placebo. The benefit over placebo was maintained at the 45-day followup, but disappeared by 90 days. The ADAS-Cog13 did not differ at end of treatment, but was worse in the treated group at day 45. Increases in blood immune cells and proinflammatory cytokines were confirmed, consistent with GM-CSF’s immune modulatory activity. Plasma Aβ, tau, and the neurodegeneration marker UCHL1 significantly moved toward normal during treatment, then returned to baseline in the followup. Trial results were published after peer review (Potter et al., 2021).

In 2016, the Colorado investigators received an Alzheimer's Association Part the Cloud grant for a Phase 2 study testing a longer, six-month treatment.

In 2013, the National Institute on Aging awarded funding for a Phase 2 trial to be conducted by Sanofi Aventis to evaluate sargramostim for its ability to clear amyloid deposits and affect cognition in patients with mild cognitive impairment (Feb 2014 news). This study started in November 2016 and anticipated enrolling 30 people 40 or older who meet NIA-AA criteria for MCI due to AD and have a positive amyloid PET scan. This study was to evaluate a six-month course of subcutaneous injection of sargramostim or placebo for reduction of brain amyloid as measured by change in florbetabir retention. Secondary outcome measures were to include safety, CSF analysis, MRI to look for ARIA, and measurement of antibodies against sargramostim. This study was to be conducted in Houston but was withdrawn prior to enrollment due to slow recruitment.

For details, see

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031
Sanofi NCT02667496

Last Updated: 10 May 2021


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News Citations

  1. At AAIC, Yet Another Phase 3 Flop While Phase 1 Trials Forge Ahead
  2. New Initiative AMPs Up Alzheimer’s Research

Paper Citations

  1. . Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimers Dement (N Y). 2021;7(1):e12158. Epub 2021 Mar 24 PubMed.
  2. . Macrophage colony-stimulating factor augments beta-amyloid-induced interleukin-1, interleukin-6, and nitric oxide production by microglial cells. J Biol Chem. 1998 Aug 14;273(33):20967-71. PubMed.
  3. . GM-CSF upregulated in rheumatoid arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice. J Alzheimers Dis. 2010;21(2):507-18. PubMed.
  4. . Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice. J Neuroimmunol. 2018 Jun 15;319:80-92. Epub 2018 Mar 17 PubMed.
  5. . Neutralization of granulocyte macrophage colony-stimulating factor decreases amyloid beta 1-42 and suppresses microglial activity in a transgenic mouse model of Alzheimer's disease. Hum Mol Genet. 2009 Oct 15;18(20):3876-93. PubMed.
  6. . Distribution of granulocyte-monocyte colony-stimulating factor and its receptor α-subunit in the adult human brain with specific reference to Alzheimer's disease. J Neural Transm. 2012 Mar 20; PubMed.
  7. . Granulocyte Macrophage Colony Stimulating Factor Treatment is Associated with Improved Cognition in Cancer Patients. Brain Disord Ther. 2012;1(1) PubMed.

External Citations

  1. Part the Cloud

Further Reading


  1. . GM-CSF upregulated in rheumatoid arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice. J Alzheimers Dis. 2010;21(2):507-18. PubMed.
  2. . Granulocyte-macrophage colony-stimulating factor is neuroprotective in experimental traumatic brain injury. J Neurotrauma. 2014 May 15;31(10):976-83. Epub 2014 Mar 7 PubMed.
  3. . Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer's disease mice. J Cereb Blood Flow Metab. 2016 Nov;36(11):1978-1991. Epub 2016 Jul 21 PubMed.