An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety, tolerability, and immune biomarkers from limited case numbers

BACKGROUND: The clinical utility and safety of sargramostim has previously been reported in cancer, acute radiation syndrome, autoimmune disease, inflammatory conditions, and Alzheimer’s disease. The safety, tolerability, and mechanisms of action in Parkinson’s disease (PD) during extended use has not been evaluated. METHODS: As a primary goal, safety and tolerability was assessed in five PD patients treated with sargramostim (Leukine(®), granulocyte–macrophage colony-stimulating factor) for 33 months. Secondary goals included numbers of CD4(+) T cells and monocytes and motor functions. Hematologic, metabolic, immune, and neurological evaluations were assessed during a 5-day on, 2-day off therapeutic regimen given at 3 μg/kg. After 2 years, drug use was discontinued for 3 months. This was then followed by an additional 6 months of treatment. RESULTS: Sargramostim-associated adverse events included injection-site reactions, elevated total white cell counts, and bone pain. On drug, blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment. Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased. In the initial 6 months of treatment, transcriptomic and proteomic monocyte tests demonstrated autophagy and sirtuin signaling. This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms. CONCLUSIONS: Taken together, the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment. Confirmation in larger patient populations is planned in a future phase II evaluation. Trial registration: ClinicalTrials.gov: NCT03790670, Date of Registration: 01/02/2019, URL:https://clinicaltrials.gov/ct2/show/NCT03790670?cond=leukine+parkinson%27s&draw=2&rank=2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40035-023-00361-1.