AD/PD 2022 | Targeting α-synuclein as a therapy for Parkinson’s disease: strategies in the pipeline

α-synuclein remains a major target for the development of novel therapeutics for Parkinson’s disease. The protein makes up Lewy bodies, the neuropathological hallmark of PD, and has been widely linked to synaptic dysfunction, mitochondrial disruption, lysosomal pathway dysregulation, oxidative stress, and ultimately, neurodegeneration. Tiago Outeiro, PhD, University Medical Center Göttingen, Göttingen, Germany, discusses several α-synuclein-targeted therapeutic approaches under investigation. Immunotherapy has been the most studied to date, although several promising clinical trials ended in termination after failing to meet prespecified endpoints. The use of small molecules in order to target alpha-synuclein aggregation is another angle under investigation. Since α-synuclein gene duplications and triplications lead to Parkinson’s disease, a potential therapeutic approach is to reduce α-synuclein production to prevent accumulation. Antisense oligonucleotides are being developed to this end. It is likely therapeutic efforts will need to address several angles of α-synuclein toxicity, targeting spread, production, and aggregation at the same time. This interview took place at the AD/PD™ 2022 Conference in Barcelona, Spain.