Peter A. LeWitt, MD

Professor of Neurology, Sastry Foundation Endowed Chair in Neurology, Wayne State University

 “Update on Parkinson disease: drugs, bugs, and TUGs”

Abstract

The neuroscience identity of Parkinson disease (PD) has evolved greatly in in the past half-century. Therapeutics have advanced beyond dopamine replacement therapy to drugs operating on other neurotransmitter systems. Symptomatic pharmaceutical therapy for PD has been augmented in the past 30 years by the advent of pulsed electrical stimulation targeted at specific sites of brain circuitry. Cellular implantation therapies have shown favorable proof-of concept outcomes (though without practical implications at this point). Several gene therapy approaches for PD have been investigated; for one of them, neuronal neurochemical phenotype was transformed from glutaminergic to GABAergic neurotransmission. Following discovery of the first genetic form of Parkinsonism 3 decades ago (an alpha-synuclein gene mutation), >2 dozen genetic forms of PD have been recognized. With identification of pathogenic misfolded alpha-synuclein as a key step in the pathogenesis of PD, multiple mechanisms of neuronal dysfunction in PD have been investigated. Findings so far raise the strong possibility that the clinical syndrome of PD might have multiple etiologies. As a result, research into this relatively common neurodegenerative disease remains an ongoing challenge for the neuroscience and clinician community alike as better symptomatic and disease-modifying therapies are sought.