Sargramostim boosts regulatory T cells

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Howard Gendelman, R. Lee Mosley and colleagues, University of Nebraska Medical Center (UNMC); the drug is Leukine (sargramostim), made by Partner Therapeutics, which is a registered collaborator.

What happened

• Phase 1 (npj Parkinson's Disease 2017). 20 people with Parkinson's, randomised to sargramostim 6 µg/kg a day or placebo by self-injection for 56 days, with 17 age-matched healthy controls. Adverse events occurred in 10 of 10 on the drug and 8 of 10 on placebo (injection-site reactions, raised white cell counts, bone pain); one hives reaction and one vasculitis reaction were linked to the drug or its preservative, and one person with a history of cerebrovascular disease had a stroke. Regulatory T-cell number and function rose on the drug. Part III motor scores (UPDRS) showed modest improvement against placebo at weeks 6 and 8. The authors say larger studies are needed.
• 12-month study (Olson et al., EBioMedicine 2021; NCT03790670). Open-label Phase 1b, five people on 3 µg/kg a day, five days a week. The lower dose caused fewer and milder adverse events than 6 µg/kg. Regulatory T cells rose and MDS-UPDRS part III did not worsen (scores fell, with no placebo group). The 2021 UNMC release's dose figure (125 µg/mm²) was not found in the paper and was dropped.
• Longer follow-up (Olson et al., Transl Neurodegener 2023). The same five people were treated for 33 months (with a 3-month break after two years). Safety held, UPDRS scores stayed stable and regulatory T cells stayed raised. The authors plan a Phase 2 to confirm.
• Later work. NCT05677633, open-label Phase 1 at 3 µg/kg for 48 weeks to validate blood biomarkers: registry says completed (11 enrolled, ended Nov 2024), no results posted.

Why it moved us toward a cure

Landmark 38 showed patients' T cells react to synuclein. If immune damage drives loss of neurons, calming it with regulatory T cells is a way to slow the disease. This is the first human test of that idea in Parkinson's I found.

Outcome

Open. Biologically active and tolerated at the lower dose, but the clinical signals come from tiny uncontrolled data. I found no registered Phase 2.

Sources

• Gendelman et al., npj Parkinsons Dis 2017, DOI 10.1038/s41531-017-0013-5
• Olson et al., EBioMedicine 2021, DOI 10.1016/j.ebiom.2021.103380 (PMID 34000620) · Olson et al., Transl Neurodegener 2023, DOI 10.1186/s40035-023-00361-1 (PMID 37217980)
• Abstracts read via Europe PMC. NCT03790670 · NCT05677633
• UNMC news, 19 May 2021 (not re-read)
• Not yet verified: the motor-score changes in the 2021 and 2023 papers (abstracts give no numbers); NCT05677633 results; any funded Phase 2.