J D Rollnik1. 1. Institut für neurorehabilitative Forschung (InFo) der BDH-Klinik Hessisch Oldendorf gGmbH, Assoziiertes Institut der Medizinischen Hochschule Hannover (MHH), Greitstr. 18-28, 31840, Hessisch Oldendorf, Deutschland, prof.rollnik@bdh-klinik-hessisch-oldendorf.de.
Abstract
BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by hyperkinetic movements, psychiatric (e.g. depression and psychosis) and cognitive symptoms (frontal lobe dementia). In Germany approximately 8000 patients suffer from HD. OBJECTIVES: The paper reviews the clinical course, epidemiology, genetics, differential diagnoses, pathophysiology, symptomatics and causal treatment options. METHODS: Publications on animal and human HD studies and trials and reviews available in Medline have been taken into account. RESULTS: Only genetic testing allows diagnostic certainty. The CAG repeat length influences age of onset, disease course and life expectancy. The mechanism by which mutant huntingtin protein (mHTT) causes HD is complex and poorly understood but leads to cell death, in particular in striatal neurons. In clinical trials antioxidants (e.g. coenzyme Q10), selisistat, PBT2, cysteamine, N-methyl-D-aspartate (NMDA)-receptor antagonists and tyrosine kinase B receptor agonists have been studied in HD. CONCLUSION: No disease-modifying therapy is currently available for HD; however, gene silencing, e.g. through RNA interference, is a promising technique which could lead to effective therapies in due course.
BACKGROUND:Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by hyperkinetic movements, psychiatric (e.g. depression and psychosis) and cognitive symptoms (frontal lobe dementia). In Germany approximately 8000 patients suffer from HD. OBJECTIVES: The paper reviews the clinical course, epidemiology, genetics, differential diagnoses, pathophysiology, symptomatics and causal treatment options. METHODS: Publications on animal and humanHD studies and trials and reviews available in Medline have been taken into account. RESULTS: Only genetic testing allows diagnostic certainty. The CAG repeat length influences age of onset, disease course and life expectancy. The mechanism by which mutant huntingtin protein (mHTT) causes HD is complex and poorly understood but leads to cell death, in particular in striatal neurons. In clinical trials antioxidants (e.g. coenzyme Q10), selisistat, PBT2, cysteamine, N-methyl-D-aspartate (NMDA)-receptor antagonists and tyrosine kinase B receptor agonists have been studied in HD. CONCLUSION: No disease-modifying therapy is currently available for HD; however, gene silencing, e.g. through RNA interference, is a promising technique which could lead to effective therapies in due course.
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Authors: Paul C Trippier; Kristin Jansen Labby; Dustin D Hawker; Jan J Mataka; Richard B Silverman Journal: J Med Chem Date: 2013-03-27 Impact factor: 7.446
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Authors: Sigurd D Süssmuth; Salman Haider; G Bernhard Landwehrmeyer; Ruth Farmer; Chris Frost; Giovanna Tripepi; Claus A Andersen; Marco Di Bacco; Claudia Lamanna; Enrica Diodato; Luisa Massai; Daniela Diamanti; Elisa Mori; Letizia Magnoni; Jens Dreyhaupt; Karin Schiefele; David Craufurd; Carsten Saft; Monika Rudzinska; Danuta Ryglewicz; Michael Orth; Sebastian Brzozy; Anna Baran; Giuseppe Pollio; Ralph Andre; Sarah J Tabrizi; Borje Darpo; Goran Westerberg Journal: Br J Clin Pharmacol Date: 2015-03 Impact factor: 4.335