2021 Volume 38 Issue 3 Pages 264-268
Aggregation of α–synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD). Reduction of αSyn production may provide a disease–modifying therapy in PD. ASOs designed against human SNCA have the potential to be a disease–modifying therapeutic target for PD patients. PARK4 patients with a duplication or triplication of the αSyn gene, without any pathological mutation, are healthy before onset, although their symptoms develop relatively early. PARK4 might be a useful target to investigate the mechanism through which DA neurons regulate αSyn aggregation before the clinical onset of PD and could lead to the development of new therapies for patients with PARK4. Inhibition of leucine–rich repeat kinase 2 (LRRK2) activity also represents one of the most promising therapeutic strategies. A phase I clinical study evaluating the safety and tolerability is currently enrolling 82 subjects in Europe. For the development of these therapies, it is important to provide an accurate diagnosis at a very early stage of the disease and it is necessary to develop accurate biomarkers that can be used to assess the degree of the accumulation of α–synuclein aggregates in the brain of patients to evaluate the efficacy of those treatments.
