Phase 1/2a Open-Label Ascending Dose Study to Evaluate the Safety and Effects of LY3884961 in Patients with Parkinson’s Disease with at Least One GBA1 Mutation (PROPEL)

Parkinson’s disease is a slowly progressive and disabling disease of the central nervous system that causes problems with movement, such as shaking, stiffness, slow movement, and difficulty walking. Patients may also experience other symptoms, such as difficulty with memory and/or thinking skills, problems with mood, and sleep disturbances, as well as other symptoms including, but not limited to, pain and constipation. It is estimated that 5%-25% of patients with Parkinson’s disease carry mutation(s) of the GBA1 gene. The GBA1 gene controls production of a specific protein in the body, which plays a role in the removal of waste from cells. When the GBA1 gene is altered, the machinery for removing waste from the cells breaks down. These processes are believed to contribute to the onset and symptoms of Parkinson’s disease. People suffering from GBA-associated Parkinson’s disease typically show the same symptoms, however their disease often starts at a younger age and may cause more significant symptoms related to memory or thinking. The standard treatments for Parkinson’s disease currently include medications and deep-brain stimulation. These treatments are used to treat the symptoms of Parkinson’s disease, but there are currently no treatments that target the progression of the disease or that are specifically developed for patients who carry GBA1 mutations. The purpose of this study, which involves research, is to find out what effects, good or bad, LY3884961 has on Parkinson’s disease. LY3884961 is designed to deliver a normal GBA1 gene copy to increase the activity of an enzyme which is low in Parkinson’s disease patients with a GBA1 mutation. If successful, the GBA1 gene will remain in your body for a period that may last for the course of your lifetime. LY3884961 is an investigational gene therapy product, which means Health Authorities have not approved it for the treatment of Parkinson’s disease or any other indication. It has been tested on three human participants in this study and three human participants in another study (see section entitled “Risks Associated with Study Treatment”). It has been tested in animals where no related adverse events were observed at the dose that will be used in this clinical study.