The need for neuroprotective therapies in Parkinson's disease: a clinical perspective

Slowing of disease progression remains a major unmet need in the treatment of Parkinson's disease (PD). Multiple factors are responsible for progression of disability in this disorder including worsening of cardinal motor features due to progressive nigral pathology, the evolution of poorly levodopa-responsive symptoms like freezing, postural instability and falls as well as motor complications of sustained treatment with levodopa. In addition, non-motor symptoms including cognitive decline, autonomic failure, sleep disorders and pain become increasingly prevalent with advancing disease and add to the overall burden of this disease. So far no treatment has been shown to significantly retard the progression of overall disability, and neuroprotective trials have been limited by design issues and a narrow focus on rates of decline of motor scores or imaging markers of nigrostriatal dysfunction only. Current evidence suggests that it may soon be possible to define populations at increased risk to develop PD and thus to target the "preclinical" phase of PD for neuroprotection. Such future trials will test intervention for their ability to prevent or retard the development of clinically overt PD in at-risk individuals.