AUTHOR=Kinnunen Kirsi M. , Schwarz Adam J. , Turner Emily C. , Pustina Dorian , Gantman Emily C. , Gordon Mark F. , Joules Richard , Mullin Ariana P. , Scahill Rachael I. , Georgiou-Karistianis Nellie , The Huntington's Disease Regulatory Science Consortium (HD-RSC) , Aggarwal Varun , Ali Shazia , Antonijevic Irina , Arnesen Astri , Atassi Nazem , Beers Brian , Belluscio Beth , Har Limor Ben , Benard Angele , Benn Caroline , Bettencourt Brian , Bhattacharyya Anu , Blumenstein Robi , Borowsky Beth , Bostwick Bret , Burton Jackson , Caputo Angelika , Cooper David , Elmer Brad , Evans Rebecca , Feigen Andrew , Fisher Terrence , Fuller Rebecca , Gantman Emily , Gartner Danielle , Geva Michal , Georgiou-Karistianis Nellie , Gonzalez Sandra , Good Adam , Gordon Mark , Goyal Jaya , Hayden Michael , Herath Priyantha , Hersch Steve , Hu Jianying , Kayson Elise , Koski Eileen , Landwehrmeyer Bernhard , Lax Michelle , Leavitt Blair , Leong Dorothy , Levy Oren , Liu Enchi , Long Jeff , Macdonald Doug , Major Jacqueline , Mehta Lahar , Mestre Tiago , Miller Eric , Mueller Christian , O'Riordan Catherine , Panagoulias Jennifer , Panzara Mike , Pedata Anne , Petrillo-Billet Jennifer , Podskalny Dave , Reader Alisha , Redman Shelly , Reilmann Ralf , Romero Klaus , Ross Christopher , Rosser Anne , Sampaio Cristina , Samzelius Jan , Schobel Scott , Schwarz Adam , Sivakumaran Sudhir , Socha Jennie , Stebbins Glenn , Stout Julie , Tabrizi Sarah , Turner Emily , Venuto Charles , Vetter Louise , Viglietta Vissia , Helgren Sarah Wahlstrom , White Beth , Wild Ed , Yohrling George , Zauderer Maurice TITLE=Volumetric MRI-Based Biomarkers in Huntington's Disease: An Evidentiary Review JOURNAL=Frontiers in Neurology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.712555 DOI=10.3389/fneur.2021.712555 ISSN=1664-2295 ABSTRACT=

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.