Neuroprotective strategies in Parkinson’s disease: A long road ahead

Abstract

Neuroprotection has been a fascinating area of research in Parkinson’s disease (PD). It offers the promise of disease modification, in turn, slowing the disease progression. A vast array of agents has been assessed for its neuroprotective properties. Although many of these agents have achieved varying degrees of efficacy in preclinical models of PD, definitive success has not been observed in clinical trials. The reasons underlying the lack of success lie within the intrinsic heterogeneity of PD. Instead of using a single agent for all patients in a “one-size-fits-all” approach, it is increasingly apparent that a specific study population with a well-defined predominant pathogenic mechanism should be selected for trials, assessing the role of each agent targeting a specific mechanism. Coenzyme Q10 may find use in an enriched cohort of PD patients with PARKIN mutations. The glucagon-like peptide 1 (GLP-1) analogue, exenatide, is currently being assessed in a phase III trial. Other GLP-1 agonists, such as liraglutide, lixisenatide, and semaglutide, are undergoing phase II trials. In addition, coffee has been shown to have a nonlinear relationship with PD risk. With increasing genetic and molecular understanding of PD, the dream of neuroprotection in PD may be realized in the near future. In this review, we summarize the current evidence on neuroprotection in PD.