15 Mar Clinical Fellow
Contact: David Goldstein, firstname.lastname@example.org
Research of the Autonomic Medicine Section (AMS) focuses on autonomic and catecholamine-related disorders, using a mainly patient-oriented approach. In the prospective longitudinal PDRisk study (NIH Clinical Protocol 09N0010) we are assessing whether in individuals who have multiple risk factors for Parkinson disease (PD) biomarkers of central or cardiac catecholamine deficiency predict the development of PD during up to 7.5 years of follow-up. As part of NIH Clinical Protocol 18N0140, “Clinical Laboratory Evaluation of Chronic Autonomic Failure,” we are conducting a prospective natural history study to test the hypothesis that Lewy body neurogenic orthostatic hypotension (nOH) without signs of central neurodegeneration may evolve into PD+nOH or dementia with Lewy bodies+nOH. In this protocol we are also combining clinical catecholamine neurochemistry, 18F-dopamine sympathetic neuroimaging, and quantitative immunofluorescence microscopy to distinguish among chronic autonomic failure syndromes. In a collaborative genotype-phenotype study of alpha-synuclein/tyrosine hydroxylase colocalization in skin biopsies we are identifying which forms of familial PD are associated with peripheral intra-neuronal synucleinopathy. We are using a computational modeling approach based on homeostasis and the catecholaldehyde hypothesis for the pathogenesis of PD to predict the progression of catecholaminergic neurodegeneration in Lewy body diseases. We are applying cerebrospinal fluid catecholamine neurochemistry and multi-tracer central and peripheral neuroimaging to identify dysfunctional but extant catecholaminergic neurons—the “sick-but-not-dead” phenomenon. We are collaborating in a clinical trial of type 2 adeno-associated virus-glial cell line-derived neurotrophic factor to treat multiple system atrophy.