Abstract
Preclinical data have shown that rilmenidine can regulate autophagy in models of Huntington's disease (HD), providing a potential route to alter the disease course in patients. Consequently, a 2-year open-label study examining the tolerability and feasibility of rilmenidine in mild-moderate HD was undertaken. 18 non-demented patients with mild to moderate HD took daily doses of 1 mg Rilmenidine for 6 months and 2 mg for a further 18 months followed by a 3-month washout period. The primary outcome was the number of withdrawals and serious adverse events. Secondary outcomes included safety parameters and changes in disease-specific variables, such as motor, cognitive and functional performance, structural MRI and serum metabolomic analysis. 12 patients completed the study; reasons for withdrawal included problems tolerating study procedures (MRI, and venepuncture), depression requiring hospital admission and logistical reasons. Three serious adverse events were recorded, including hospitalisation for depression, but none were thought to be drug-related. Changes in secondary outcomes were analysed as the annual rate of change in the study group. The overall change was comparable to changes seen in recent large observational studie...Continue Reading
References
Jan 1, 1979·Neurology·I Shoulson, S Fahn
Sep 1, 1994·Journal of Clinical Epidemiology·W A KukullM L Pfanschmidt
Sep 1, 1994·Dementia·T W RobbinsP Rabbitt
Aug 1, 1993·Nature Genetics·S E AndrewM A Kalchman
Feb 11, 2000·Neurology·K MarderI Shoulson
Dec 22, 2005·Human Molecular Genetics·Zdenek BergerDavid C Rubinsztein
Feb 9, 2006·Brain : a Journal of Neurology·Benjamin R UnderwoodDavid C Rubinsztein
Sep 16, 2006·Molecular Aspects of Medicine·Brinda Ravikumar, David C Rubinsztein
Feb 12, 2010·The Journal of Biological Chemistry·Maurizio RennaDavid C Rubinsztein
Mar 2, 2010·Human Molecular Genetics·Claudia RoseDavid C Rubinsztein
Nov 12, 2010·Neurology·N BechtelR Reilmann
Dec 7, 2010·Lancet Neurology·Sarah J TabriziUNKNOWN TRACK-HD Investigators
Dec 6, 2011·Lancet Neurology·Sarah J TabriziUNKNOWN TRACK-HD investigators
Feb 24, 2012·PloS One·UNKNOWN Huntington Study Group COHORT Investigators, E Ray Dorsey
Mar 13, 2013·JAMA Neurology·E Ray DorseyKevin M Biglan
May 15, 2013·Lancet Neurology·Sarah J TabriziUNKNOWN TRACK-HD Investigators
Nov 5, 2015·Expert Opinion on Pharmacotherapy·Sarah L Mason, Roger A Barker
Citations
May 7, 2020·Autophagy·Per Ludvik BrattåsKarolina Pircs
Mar 16, 2018·Metabolic Brain Disease·Karolina PierzynowskaGrzegorz Węgrzyn
Apr 30, 2019·Frontiers in Neuroscience·Yanfeng JiangXingdong Chen
Jan 1, 2020·Brain Sciences·Laura B FergusonRobert O Messing
Mar 10, 2020·Journal of Neurochemistry·Olga CortiPhilip M Beart
Aug 29, 2018·Brain Plasticity·Karolina PircsJohan Jakobsson
Jan 15, 2019·Journal of Huntington's Disease·Melanie P Jensen, Roger A Barker
Feb 8, 2019·Cell Death and Differentiation·Maria Chiara Maiuri, Guido Kroemer
Apr 3, 2021·Neurobiology of Disease·Nirma D PereraBradley J Turner
Jul 10, 2021·Autophagy·Muhammed KocakOle Pless
Aug 28, 2021·International Journal of Molecular Sciences·Amy KimJoana Gil-Mohapel