Frontiers in Neurology (Sep 2021)

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

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

DOI
https://doi.org/10.3389/fneur.2021.712555
Journal volume & issue
Vol. 12

Abstract

Read online

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.

Keywords