Parkinson Disease: Galpern WR

Galpern WR, Cudkowicz ME. · National Institute of Neurological Disorders and Stroke, National Institutes of Health, 6001 Executive Blvd., Room 2225, Bethesda, MD 20892, USA. · Mitochondrion. · Pubmed #17485247 No free full text.

Abstract: The etiology of several neurodegenerative disorders is thought to involve impaired mitochondrial function and oxidative stress. Coenzyme Q-10 (CoQ10) acts both as an antioxidant and as an electron acceptor at the level of the mitochondria. In several animal models of neurodegenerative diseases including amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease, CoQ10 has shown beneficial effects. Based on its biochemical properties and the effects in animal models, several clinical trials evaluating CoQ10 have been undertaken in many neurodegenerative diseases. CoQ10 appears to be safe and well tolerated, and several efficacy trials are planned.

Thomsen TR, Galpern WR, Asante A, Arenovich T, Fox SH. · Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. · Mov Disord. · Pubmed #17876852 No free full text.

Abstract: Sialorrhea is a significant problem in advanced Parkinson's disease (PD). Current treatment options include systemic anticholinergics which frequently cause side effects. We hypothesized that sublingual application of ipratropium bromide spray, an anticholinergic agent that does not cross the blood brain barrier, may reduce drooling without systemic side effects. We performed a randomized, double blind, placebo-controlled, crossover study in 17 subjects with PD and bothersome drooling. Patients were randomized to receive ipratropium bromide or placebo (one to two sprays, maximum of four times per day) for 2 weeks followed by a 1 week washout and crossover for further 2 weeks of treatment. The primary outcome was an objective measure of weight of saliva production. Secondary outcomes were subjective rating of severity and frequency of sialorrhoea using home diaries, United Parkinson's Disease Rating Scale (UPDRS) part II salivation subscore, parkinsonian disability using UPDRS, and adverse events. Ipratropium bromide spray had no significant effect on weight of saliva produced. There was a mild effect of treatment on subjective measures of sialorrhea. There were no significant adverse events. Ipratropium bromide spray was well tolerated in subjects with PD. Although it did not affect objective measures of saliva production, further studies in parkinsonism may be warranted.

Tilley BC, Galpern WR. · Department of Biostatistics, Bioinformatics & Epidemiology, Medical University of South Carolina, Charleston, SC 29425. · Stroke. · Pubmed #17261742 links to  free full text

Abstract: In Parkinson Disease (PD) as well as in stroke research there is an urgent need to both optimize the use of resources (number of patients, costs, and time) and select potential effective neuroprotective agents. The processes used to identify and study new therapies for PD may be applicable to the search for new therapies in stroke. The National Institute of Neurological Disorders and Stroke (NINDS) organized the Committee to Identify Neuroprotective Agents for Parkinson's (CINAPS). CINAPS broadly solicited suggestions for agents and evaluated these agents using rigorous criteria. NINDS also created the NIH Exploratory Trials in PD program (NET-PD), a clinical network where CINAPS recommendations could be tested. Given multiple recommended agents, NET-PD investigators used Phase II futility designs with calibration controls, tested against an historical standard, to screen agents for testing in Phase III trials. Investigators also used the Phase II trial to assess ancillary outcome measures for use in Phase III. The observed value for the calibration controls in the first NET-PD Phase II trial was outside the 95% CI for the historical standard. Using bootstrap methodology it appeared unlikely this outcome happened by chance. The historical standard was updated using more contemporaneous data than were available at the start of the futility trials and a re-evaluation using the new threshold was conducted. Assessment of ancillary outcome measures led to a reduced set of outcome measures for use in Phase III. The CINAPS process, and lessons learned from NET-PD futility studies, particularly with respect to calibration controls and assessment of outcome measures, could enhance the choice and testing of new agents for stroke treatment.