Clinical trials of neuroprotection for Parkinson's disease.

Abstract

In the concluding pages of the first monograph to describe Parkinson’s disease (PD), we read that: … Until we are better informed respecting the nature of the disease, the employment of internal medicines is scarcely warrantable; unless analogy should point out some remedy the trial of which rational hope might authorize. Particular circumstances might arise in different cases, in which the aid of medicine may be demanded … James Parkinson, M.D. An Essay on the Shaking Palsy (1817)1 As in Parkinson’s day, the challenge is still with us to find rational therapeutic interventions for this disorder. Lacking evidence that points to the cause (or causes) of PD, contemporary efforts to slow or halt the disease are guided primarily by analogies to animal models and the few available insights into the pathophysiology of this disorder. Nevertheless, a long list of hypothetical targets for definitive treatment of PD has been developed. Reflecting this diversity of options, a recent initiative by the National Institutes of Health in the United States has considered 59 choices for protective therapies against the progression of PD.2 The range of possible anti-PD therapies is far greater today than the limited focus on antioxidant therapies two decades ago. This article reviews the results of several clinical trials along with comments regarding ongoing studies of neuroprotection in PD. The motor impairments of PD are generally progressive over time, and several types of evidence link the clinical deterioration to loss of dopaminergic neurons projecting to the striatum. The neuropathologic substrate of parkinsonism, whether resulting from the idiopathic disorder or from various neurotoxins that closely simulate the human motor impairments of PD, is the loss of most dopaminergic neurons in the substantia nigra pars compacta (SNpc).3 The severity of parkinsonian features appears to be in direct proportion to neuronal …