Can the disease course in Parkinson’s disease be slowed?

Amos D. Korczyn, Sharon Hassin-Baer

The diagnosis of Parkinson's disease (PD), which is needed for useful symptomatic therapy, is based on clinical criteria. However, it became quite clear in recent years that the same features can occur through different etiopathogenic mechanisms. Even a pathological diagnosis of PD, based on the demonstration of α-synuclein deposits in a typical distribution, can result from different causes and, vice versa, nigral cell loss can occur without α-synuclein deposition. Thus far, attempts to influence the progression of PD have failed. However, since the clinical manifestations of PD can be the result of diverse mechanisms, a single intervention may not be able to slow the course of the disease in all patients. Indeed, targeting the underlying pathogenic processes, which differ among cases, may be more effective. PD may develop as a consequence of mitochondrial damage, which itself may result from a variety of genetic or environmental factors. Correction of the ensuing oxidative stress may theoretically be useful in these PD patients, but will not affect the progression of the disease among other PD patients in whom an identical clinical syndrome derives from defects in other pathways such as the ubiquitin-proteasome system and lysosomal dysfunction, among others. Precision medicine can now be used to identify the underlying pathogenic mechanisms in individual patients, paving the way to the development of real disease modification through a pathway-oriented approach, aimed at the underlying biologic processes of disease occurrence and evolution.