Volumetric MRI-Based Biomarkers in Huntington's Disease: An Evidentiary Review

Frontiers in Neurology

Anne Rosser¹  Robi Blumenstein¹  Eric Miller¹  Dorothy Leong¹  Sarah Wahlstrom Helgren¹  George Yohrling¹  Jennie Socha¹  Sudhir Sivakumaran¹  Christopher Ross¹  Brian Bettencourt¹  Jianying Hu¹  Sarah Tabrizi¹  Rebecca Fuller¹  Michal Geva¹  Blair Leavitt¹  Beth Borowsky¹  Nazem Atassi¹  Doug Macdonald¹  Bernhard Landwehrmeyer¹  Jan Samzelius¹  Danielle Gartner¹  Adam Schwarz¹  Glenn Stebbins¹  Varun Aggarwal¹  Catherine O'Riordan¹  Jeff Long¹  Jaya Goyal¹  Christian Mueller¹  Julie Stout¹  Sandra Gonzalez¹  Shazia Ali¹  Elise Kayson¹  Enchi Liu¹  Scott Schobel¹  Adam Good¹  Oren Levy¹  Ralf Reilmann¹  Vissia Viglietta¹  Mark Gordon¹  Angelika Caputo¹  Jackson Burton¹  Brad Elmer¹  Terrence Fisher¹  Beth White¹  Steve Hersch¹  Michelle Lax¹  Ed Wild¹  Angele Benard¹  Maurice Zauderer¹  Nellie Georgiou-Karistianis¹  Jacqueline Major¹  Anne Pedata¹  Jennifer Petrillo-Billet¹  Klaus Romero¹  Brian Beers¹  David Cooper¹  Bret Bostwick¹  Dave Podskalny¹  Shelly Redman¹  Rebecca Evans¹  Priyantha Herath¹  Lahar Mehta¹  Alisha Reader¹  Louise Vetter¹  Emily Gantman¹  Emily Turner¹  Irina Antonijevic¹  Eileen Koski¹  Jennifer Panagoulias¹  Michael Hayden¹  Andrew Feigen¹  Cristina Sampaio¹  Astri Arnesen¹  Charles Venuto¹  Limor Ben Har¹  Mike Panzara¹  Beth Belluscio¹  Caroline Benn¹  Anu Bhattacharyya¹  Tiago Mestre¹  Dorian Pustina²  Emily C. Gantman²  The Huntington's Disease Regulatory Science Consortium (HD-RSC)³  Emily C. Turner³  Rachael I. Scahill⁴  Kirsi M. Kinnunen⁵  Richard Joules⁵  Adam J. Schwarz⁷  Mark F. Gordon⁸  Ariana P. Mullin⁹ 

[1] ;CHDI Management/CHDI Foundation, Princeton, NJ, United States;Critical Path Institute, Tucson, AZ, United States;Huntington's Disease Research Centre, UCL Institute of Neurology, London, United Kingdom;IXICO, London, United Kingdom;School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia;Takeda Pharmaceuticals, Ltd., Cambridge, MA, United States;Teva Pharmaceuticals, West Chester, PA, United States;Wave Life Sciences, Ltd., Cambridge, MA, United States;

关键词: Huntington's disease;    neurodegenerative;    biomarkers;    neuroimaging;    volumetric MRI;    C-Path;   

DOI  :  10.3389/fneur.2021.712555

来源: DOAJ

【 摘 要 】

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community—biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations—to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.

【 授权许可】

Unknown