Long-Term Low-Dose Sargramostim Therapy Restores Immune Homeostasis in Parkinson Disease

Parkinson disease
Parkinson disease
Because sargramostim therapeutic use has been offset by dose-dependent adverse events, the researchers performed a reduced drug dose regimen to evaluate safety and to discover novel disease-linked biomarkers during sargramostim treatments for 1 year.

Immune homeostasis was restored among patients with Parkinson disease (PD) after long-term sargramostim therapy. These findings from a phase 1b study were published in EBioMedicine.

Patients (N=5) with PD were recruited at the University of Nebraska Medical Center to assess the safety and tolerability of sargramostim. For 3 months, patients received 3 mg/kg/day subcutaneous sargramostim, 5 days a week.

Patients had a mean age of 64 (standard deviation [SD], 5) years, all were men, all were White, average time since PD diagnosis was 8 (SD, 5) years, all were on carbidopa-levodopa therapies, and their average unified PD rating scale part (UPDRS III) score was 20 (SD, 5) points.

All patients reported at least 1 adverse event. Elevated white blood cell counts were observed among all patients, 4 had injection site reactions, 3 had a fall injury, and 3 had nausea. Although 2 severe adverse events occurred, they were not associated with the study drug.

Compared with the phase 1a study, which used a higher dose (6 mg/kg/day), the lower dose was associated with fewer injection site reactions, chest pain, soreness, weakness, and itching (P =.0070) as well as a decrease in the severity of adverse events (P =.0304).

There was a trend for UPDRS III scores to decrease over time (P =.0407).

After sargramostim therapy, more CD4+ lymphocytes expressed forkhead box P3 (FOXP3), cytotoxic T-lymphocyte-associated protein 4 (CTLA), integrin subunit beta 7 (ItgB7), ItgA4B7, Helios, and CD31 and more Treg subsets had elevated CD45RO, CD31, CD49, CTLA4, and ItgB7. Demethylation among Treg isolates was increased by 20% at 2 months.

Treg-mediated activity correlated with FOXP3 demethylation (r, 0.3212; P =.0004), integrin B7+/CD4+ (r, 0.3189; P =.0385), FOXP3+/CD4+ (r, 0.3019; P =.0426), FAS+/CD4+ (r, 0.2840; P =.0426), CD45RA-RO+/CD4+ (r, 0.2799; P =.0426), CD27+CCR7-/Treg (r, 0.3468; P =.0254), integrin B7+/Treg (r, 0.3537; P =.0254), Integrin A4B7/Treg (r, 0.2735; P =.0426), and CD45RA-CD27+CCR7-/Treg (r, 0.2733; P =.0426).

UPDRS III scores correlated with FAS+/CD4+ (r, -0.7321; P =.0004), integrin B7/Treg (r, -0.4491; P =.0004), CD45RA+CD27+CCR7-/Treg (r, -0.3685; P =.0014), CD27+CCR7-/Treg (r, -0.3366; P =.0025), and inhibitory Treg number (r, 0.2500; P =.0104).

This study was limited by its lack of ethnic and gender diversity.

These data indicated long-term, low-dose sargramostim therapy was well tolerated, PD severity was not increased, and immune homeostasis was restored.


Olson KE, Namminga KL, Lu Y, et al. Safety, tolerability, and immune-biomarker profiling for year-long sargramostim treatment of Parkinson’s disease. EBioMedicine. Published online May 14, 2021. doi:10.1016/j.ebiom.2021.103380