Present and future disease–modifying therapy for Parkinson disease

Abstract

Parkinson disease (PD) is characterized by the appearance of intracellular neuronal inclusions (i.e., Lewy bodies, LB) composed mainly of misfolded α–synuclein (αS). Under physiological state, αS is a small protein with no specific higher–order structure ; however, it begins to aggregate and acquire toxicity by gene mutation/duplication and various physico–chemical stresses. Therefore, many disease–modifying therapies for LB diseases/synucleinopathies have focused on reducing or eliminating abnormally aggregated, noxious αS. In this paper, I will first focus on the αS antibody therapies, which have attracted particular attention among disease–modifying therapies in synucleinopathy, and then discuss about the importance of patient stratification, which is a key for the success of clinical trials.