Adults with mild to moderate Parkinson’s disease showed reductions in free serum alpha-synuclein levels without notable side effects after intravenous treatment with a monoclonal antibody known as PRX002.
“Pathologically, PD [Parkinson’s disease] is typically associated with an accumulation of aggregated alpha-synuclein protein in the central nervous system and the peripheral nervous system,” making alpha-synuclein a target for treatment in preclinical studies, wrote Joseph Jankovic, MD, of Baylor College of Medicine, Houston, and his colleagues.
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“Notably, rapid and robust reductions in free serum alpha-synuclein levels were achieved without seriously affecting safety,” the researchers said. Overall, reductions in free serum alpha-synuclein occurred quickly and were similar throughout the study period, and treatment with PRX002 was safe, well tolerated, and effective at doses up to 60 mg/kg.
The most relevant adverse events were mild to moderate infusion-related reactions in four patients in the highest-dose group; two of these patients discontinued the study. No anti-PRX002 antibodies were seen, and no serious adverse events or deaths occurred during the study period.
Statistically significant reductions from baseline were noted at 1 and 4 hours after the first and third infusion in all dose groups, compared with placebo, and these reductions lasted longer after the higher doses.
Over the longer term, statistically significant reductions after the third infusion were noted at day 64 for the 1.0-mg/kg through 60-mg/kg dose groups, day 71 for the 1.0-mg/kg through 60-mg/kg dose groups, and at day 85 for the 3-mg/kg through 60-mg/kg dose groups.
The study findings were limited by several factors, including the relatively small sample size, short period of exposure to the treatment, homogeneous population, and lack of imaging to monitor brain pathology, the researchers noted. However, the results support the safety of PRX002 and the progression of the follow-up phase 2 study known as PASADENA.
The study was funded by Prothena Biosciences and F. Hoffmann-LaRoche. Lead author Dr. Jankovich disclosed relationships with both of those companies and has received funding from the Parkinson’s Foundation. Many of the other authors are employees of Prothena Biosciences or F. Hoffmann-LaRoche or a subsidiary.
SOURCE: Jankovic J et al. JAMA Neurol. 2018 June 18. doi: 10.1001/jamaneurol.2018.1487.