Sargramostim Improves Motor Symptoms of Parkinson Disease in Small Phase 1 Trial

An investigator-initiated clinical trial (NCT03790670) evaluated the use of sargramostim (Leukine; Partner Therapeutics, Lexington, MA). Improvements in MDS-UPDRS Part 3 scores, which measure motor symptoms, were seen in individuals with Parkinson disease (PD) who took sargramostim. 

Improved MDS-UPDRS Part 3 scores were observed in 4 of the 5 participants and the fifth had no progression in motor symptoms, reflected as no change MDS-UPDRS Part 3 score over 12 months. MDS-UPDRS Part 3 scores improved by a mean 4 points, compared with the mean 2.4-point decrease typically seen over 12 months in participants in people with PD receiving standard therapy. 

". . .disease progression was altered and the drug safely administered for one year," said Howard Gendelman, MD, chair of the University of Nebraska Medical Center (UNMC) Department of Pharmacology and Experimental Neurology (PEN) and co-lead researcher. "Additional research is required in a larger clinical study before definitive conclusions can be made for drug effectiveness."

For the study, 5 participants were enrolled and received 125 mcg/mm2 of sargramostim subcutaneously on a 5-day-on, 2-day-off regimen. All 5 participants completed the 12-month period of treatment. There was an extension at participants and investigator's request to 24 months and the number of participants increased to 10. Sargramostim was well-tolerated by participants during the 12-month treatment period with no treatment-related serious adverse. The adverse events observed were significantly less frequent and of less severity than those reported in a prior placebo-controlled study that used a higher dose (250 mcg/mm2 every day). Sargramostim treatment improved also immune function, enhanced T-regulatory cell numbers and function, and increased hypomethylation of upstream FOXP3.

"Congratulations to Dr. Gendelman and the team at UNMC for their ground-breaking pre-clinical and clinical work demonstrating Leukine's activity in restoring immune homeostasis and reducing neuroinflammation by enhancing the protective effects of Tregs", said John McManus, chief business officer at Partner Therapeutics. "Importantly, Leukine's effects on Tregs and neuroinflammation translated into improvement in motor function in these patients. Our next step is to submit an IND for PD and then initiate a phase 2, randomized, double-blind, placebo-controlled multisite study to confirm these results in a larger population of patients. Patients with PD have no treatment options that halt or reverse disease progression and we consider it a matter of urgency to accelerate Leukine's clinical development to provide a potential solution."