Early diagnosis and therapy of Parkinson’s disease: can disease progression be curbed?

Abstract

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the loss of dopamine (DA) neurons in the substantia nigra (SN). Currently, there are numerous therapeutic drugs for the treatment of PD; however, they are limited in efficacy and primarily target motor symptoms. Furthermore, these drugs have various adverse effects after long-term use. Usually, PD patients begin to take anti-parkinsonian drugs when they have developed obvious motor symptoms. At that time, a significant portion of the DA neurons in SN has been lost and the biology of the disease may have already been present for over a decade. This stage of PD diagnosis underscores the need for biomarkers that accurately indicate the onset of PD in order to apply disease-modifying therapies at an earlier stage of disease. However, development of disease modifying drugs has faced many setbacks, mostly due to the ways in which clinical trials are planned and executed. In this review paper, we summarize the recent findings of genetic biomarkers such as SNCA, LRRK2, parkin, PINK1, DJ1, etc., as well as evaluate the imaging techniques such as single proton emission computed tomography and positron emission tomography for their potential in diagnosing PD at earlier stages. Clinical trial designs, along with a comprehensive analysis of neuroprotective drugs for future treatment of PD, are also reviewed.