The "long and winding road" of the disease-modifying effects of levodopa has not ended yet

Abstract

Levodopa has long been the mainstay of Parkinson's disease (PD) pharmacological therapy. Upon its introduction, symptom relief was markedly evident, and hope arose on the potential of effect on disease progression. In fact, James Parkinson did remark that there appeared “to be sufficient reason for hoping that some remedial process may ere long be discovered, by which, at least, the progress of the disease may be stopped.”2 Unfortunately, despite recent advances,3 after 2 centuries of effort and hundreds of trials evaluating dozens of different drugs, we are still to conclusively prove a “neuroprotective” or “disease-modifying” effect of any pharmacological treatment for PD.