17 Nov Clinical and Genetic Associations of Patients At Risk of Huntington Disease
MedicalResearch.com Interview with:
Kevin M. Biglan, M.D., M.P.H
Professor of Neurology and the Associate Chair for Clinical Research
Department of Neurology and the Center for Human Experimental Therapeutics
University of Rochester School of Medicine and Dentistry
Rochester, New York
Medical Research: What is the background for this study? What are the main findings?
Dr. Biglan: A therapeutic goal of research in Huntington Disease (HD) is the identification of treatments that delay the progression of disease and onset of illness in individuals at risk for developing manifest HD. Designing such efficacy trials is challenging. A major hurdle is the lack of practical primary outcome measures to assess the effect of an intervention on delaying disease onset. Use of the dichotomous endpoint of clinical diagnosis as the primary outcome requires large sample sizes and long duration of follow up in order to show a significant therapeutic effect on delaying disease onset. Continuous measures that can reliably distinguish cytosine-adenine-guanine (CAG) expanded individuals in the pre-manifest period may allow for the identification of potential disease modifying therapies using relatively smaller cohorts followed for shorter periods of time.
The Prospective Huntington At-Risk Observational Study (PHAROS) represents the largest observational study to clinically evaluate pre-manifest Huntington Disease wherein both research participants and investigators were unaware of Huntington Disease mutation status. Accordingly, PHAROS was uniquely designed to address, in an unbiased manner, those clinical features most associated with the CAG expansion during the prodromal phase in Huntington Disease. The identification of continuous outcome measures that are associated with HD in the pre-manifest period may facilitate the design and powering of future studies of potential disease modifying therapies prior to traditional motor diagnosis.
Medical Research: What should clinicians and patients take away from your report?
Dr. Biglan: In a population prior to Huntington Disease motor diagnosis, there are significant baseline motor, cognitive and behavioral differences between subjects with and without cytosine-adenine-guanine expansions. Over time, this “pre-manifest” population worsens on motor and cognitive measures. The ability of these measures in distinguishing expanded individuals from non-expanded controls suggests that these measures could be used as outcome measures in clinical trials aimed at slowing disease progression or delaying disease onset in pre-manifest Huntington Disease . However, the large sample sizes required to detect meaningful changes may not be feasible or justifiable.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Biglan: Still needed are relevant outcomes, clinical or biological, that are highly sensitive to change and of low variability among clinically unaffected individuals who have inherited the Huntington Disease mutation.
Kevin M. Biglan, M.D., M.P.H (2015). Clinical and Genetic Associations of Patients At Risk of Huntington Disease