Funded Studies
Study Rationale: Whereas motor symptoms can be well controlled by dopamine-enhancing drugs and deep brain stimulation, dementia represents a key milestone in the course of Parkinson’s disease (PD) with no effective treatments. People with PD who carry a mutation in the GBA gene display an accelerated development of cognitive impairment. The cause of cognitive decline in PD is the abnormal clumping of different proteins in nerve cells, most often alpha-synuclein. Although some with PD develop aggregates of the amyloid-beta and tau associated with Alzheimer’s disease, individuals that carry a GBA mutation lack these aggregates and instead show pronounced aggregation of alpha-synuclein.
Hypothesis: We hypothesize that treatment with Prasinezumab, an antibody that blocks the propagation of alpha-synuclein aggregates between nerve cells, can slow the cognitive decline in people with PD who carry a GBA mutation.
Study Design: Study participants will have PD and carry a GBA mutation but show a normal cognitive profile at the onset of the trial, which will be performed in eight centers across Europe. Participants will be assigned randomly to receive Prasinezumab or a placebo for 104 weeks. Neither the participants nor the investigators will know who is receiving the treatment. Detailed cognitive assessments will be conducted at the study centers and at home. At the end of the study, we will assess whether the participants who received Prasinezumab show less cognitive decline than those who received a placebo.
Impact on Diagnosis/Treatment of Parkinson’s disease: If Prasinezumab delays the development of cognitive decline in people with PD and GBA mutation, this study will represent an outstanding example of translational research and demonstrate that future clinical trials should stratify and enrich their study populations for specific biological findings such as the causing proteins.
Next Steps for Development: The company that developed Prasinezumab, F. Hoffmann-La Roche Ltd, could plan additional studies to seek official approval for Prasinezumab to be prescribed for people with PD to prevent PD dementia.