TY - JOUR
T1 - The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA)
AU - on behalf of CRC-SCA Consortium
AU - Lin, Yicheng
AU - Amokrane, Nadia
AU - Worley, Sandie
AU - Moore, Lauren R.
AU - Rosen, Andrew
AU - Crespo, Laura P.
AU - Trace, Kelsey
AU - Ashizawa, Tetsuo
AU - Billnitzer, Andrew
AU - Perlman, Susan
AU - Fisher, Aaron
AU - Bushara, Khalaf
AU - Geschwind, Michael D.
AU - Dietiker, Cameron
AU - Gomez, Christopher M.
AU - Padmanaban, Mahesh
AU - Opal, Puneet
AU - Akhtar, Rizwan S.
AU - Paulson, Henry
AU - Srinivasan, Sharan
AU - Ferng, Amy
AU - Ferrari, Frank
AU - Onyike, Chiadi U.
AU - Fishman, Ann
AU - Ying, Sarah
AU - Paul, Ashley
AU - Schmahmann, Jeremy D.
AU - Stephen, Christopher D.
AU - Gupta, Anoopum
AU - Lin, Chih Chun
AU - Subramony, S. H.
AU - Burns, Matthew
AU - Wilmot, George
AU - Duquette, Antoine
AU - Zesiewicz, Theresa
AU - Davis, Marie Y.
AU - Hamedani, Ali G.
AU - Vizcarra, Joaquin A.
AU - Pulst, Stefan M.
AU - Primeaux, Sharon
AU - Öz, Gülin
AU - Shakkottai, Vikram G.
AU - Rosenthal, Liana S.
AU - Kuo, Sheng Han
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
PY - 2025/10
Y1 - 2025/10
N2 - Hereditary ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Since 2009, the Clinical Research Consortium for the Study of Cerebellar Ataxias (CRC-SCA) has studied the natural history of common types of spinocerebellar ataxias (SCAs). The CRC-SCA is a 17-site academic collaboration supported by the National Ataxia Foundation. In 2024, the CRC-SCA expanded its scope by incorporating newly identified late-onset ataxias, including repeat expansion mutations in RFC1 and FGF14 causing Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) and SCA27B, respectively. These ongoing efforts have enriched the understanding of disease progression and facilitated access to biofluid and neuroimaging data for biomarker discovery, setting the stage for therapeutic development in hereditary ataxias. The CRC-SCA’s natural history study and biomarker collection have validated several clinical outcome assessments (COAs) to capture important aspects of hereditary ataxias. We have also developed new COAs for cognitive and patient-reported outcome measures. A key component of the study includes biofluid collection—cerebrospinal fluid, plasma, and serum—to identify molecular biomarkers for disease progression and therapeutic response. Additionally, an incorporated magnetic resonance imaging (MRI) substudy provides critical imaging biomarkers, enhancing our ability to track macro- and microstructural, chemical and functional changes in the cerebellum and relate these to clinical presentations. The comprehensive, longitudinal dataset comprising COAs, biofluid biomarkers, and neuroimaging enhances clinical trial readiness in the field and accelerates therapeutic advancements for hereditary ataxias. This review highlights the collective efforts of CRC-SCA, details the study protocol, and emphasizes the integrity and specificity of the collected data elements.
AB - Hereditary ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Since 2009, the Clinical Research Consortium for the Study of Cerebellar Ataxias (CRC-SCA) has studied the natural history of common types of spinocerebellar ataxias (SCAs). The CRC-SCA is a 17-site academic collaboration supported by the National Ataxia Foundation. In 2024, the CRC-SCA expanded its scope by incorporating newly identified late-onset ataxias, including repeat expansion mutations in RFC1 and FGF14 causing Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) and SCA27B, respectively. These ongoing efforts have enriched the understanding of disease progression and facilitated access to biofluid and neuroimaging data for biomarker discovery, setting the stage for therapeutic development in hereditary ataxias. The CRC-SCA’s natural history study and biomarker collection have validated several clinical outcome assessments (COAs) to capture important aspects of hereditary ataxias. We have also developed new COAs for cognitive and patient-reported outcome measures. A key component of the study includes biofluid collection—cerebrospinal fluid, plasma, and serum—to identify molecular biomarkers for disease progression and therapeutic response. Additionally, an incorporated magnetic resonance imaging (MRI) substudy provides critical imaging biomarkers, enhancing our ability to track macro- and microstructural, chemical and functional changes in the cerebellum and relate these to clinical presentations. The comprehensive, longitudinal dataset comprising COAs, biofluid biomarkers, and neuroimaging enhances clinical trial readiness in the field and accelerates therapeutic advancements for hereditary ataxias. This review highlights the collective efforts of CRC-SCA, details the study protocol, and emphasizes the integrity and specificity of the collected data elements.
KW - Biomarker
KW - Cerebellar ataxias
KW - Natural history study
UR - https://www.scopus.com/pages/publications/105011883370
UR - https://www.scopus.com/inward/citedby.url?scp=105011883370&partnerID=8YFLogxK
U2 - 10.1007/s12311-025-01885-0
DO - 10.1007/s12311-025-01885-0
M3 - Review article
C2 - 40679685
AN - SCOPUS:105011883370
SN - 1473-4222
VL - 24
JO - Cerebellum
JF - Cerebellum
IS - 5
M1 - 134
ER -