TY - JOUR
T1 - A biological classification of Huntington's disease
T2 - the Integrated Staging System
AU - Huntington's Disease Regulatory Science Consortium (HD-RSC)
AU - Tabrizi, Sarah J.
AU - Schobel, Scott
AU - Gantman, Emily C.
AU - Mansbach, Alexandra
AU - Borowsky, Beth
AU - Konstantinova, Pavlina
AU - Mestre, Tiago A.
AU - Panagoulias, Jennifer
AU - Ross, Christopher A.
AU - Zauderer, Maurice
AU - Mullin, Ariana P.
AU - Romero, Klaus
AU - Sivakumaran, Sudhir
AU - Turner, Emily C.
AU - Long, Jeffrey D.
AU - Sampaio, Cristina
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/7
Y1 - 2022/7
N2 - The current research paradigm for Huntington's disease is based on participants with overt clinical phenotypes and does not address its pathophysiology nor the biomarker changes that can precede by decades the functional decline. We have generated a new research framework to standardise clinical research and enable interventional studies earlier in the disease course. The Huntington's Disease Integrated Staging System (HD-ISS) comprises a biological research definition and evidence-based staging centred on biological, clinical, and functional assessments. We used a formal consensus method that involved representatives from academia, industry, and non-profit organisations. The HD-ISS characterises individuals for research purposes from birth, starting at Stage 0 (ie, individuals with the Huntington's disease genetic mutation without any detectable pathological change) by using a genetic definition of Huntington's disease. Huntington's disease progression is then marked by measurable indicators of underlying pathophysiology (Stage 1), a detectable clinical phenotype (Stage 2), and then decline in function (Stage 3). Individuals can be precisely classified into stages based on thresholds of stage-specific landmark assessments. We also demonstrated the internal validity of this system. The adoption of the HD-ISS could facilitate the design of clinical trials targeting populations before clinical motor diagnosis and enable data standardisation across ongoing and future studies.
AB - The current research paradigm for Huntington's disease is based on participants with overt clinical phenotypes and does not address its pathophysiology nor the biomarker changes that can precede by decades the functional decline. We have generated a new research framework to standardise clinical research and enable interventional studies earlier in the disease course. The Huntington's Disease Integrated Staging System (HD-ISS) comprises a biological research definition and evidence-based staging centred on biological, clinical, and functional assessments. We used a formal consensus method that involved representatives from academia, industry, and non-profit organisations. The HD-ISS characterises individuals for research purposes from birth, starting at Stage 0 (ie, individuals with the Huntington's disease genetic mutation without any detectable pathological change) by using a genetic definition of Huntington's disease. Huntington's disease progression is then marked by measurable indicators of underlying pathophysiology (Stage 1), a detectable clinical phenotype (Stage 2), and then decline in function (Stage 3). Individuals can be precisely classified into stages based on thresholds of stage-specific landmark assessments. We also demonstrated the internal validity of this system. The adoption of the HD-ISS could facilitate the design of clinical trials targeting populations before clinical motor diagnosis and enable data standardisation across ongoing and future studies.
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U2 - 10.1016/S1474-4422(22)00120-X
DO - 10.1016/S1474-4422(22)00120-X
M3 - Review article
C2 - 35716693
AN - SCOPUS:85131554102
SN - 1474-4422
VL - 21
SP - 632
EP - 644
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 7
ER -