Review

. 2025 Jul 18;24(5):134.

doi: 10.1007/s12311-025-01885-0.

The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA)

Yicheng Lin^{1

2

3}, Nadia Amokrane^{1

2}, Sandie Worley^{1

2}, Lauren R Moore⁴, Andrew Rosen⁴, Laura P Crespo⁴, Kelsey Trace⁴, Tetsuo Ashizawa⁵, Andrew Billnitzer⁵, Susan Perlman⁶, Aaron Fisher⁶, Khalaf Bushara⁷, Michael D Geschwind⁸, Cameron Dietiker⁸, Christopher M Gomez⁹, Mahesh Padmanaban⁹, Puneet Opal¹⁰, Rizwan S Akhtar¹⁰, Henry Paulson¹¹, Sharan Srinivasan¹¹, Amy Ferng¹¹, Frank Ferrari¹¹, Chiadi U Onyike¹², Ann Fishman¹², Sarah Ying¹³, Ashley Paul¹³, Jeremy D Schmahmann¹⁴, Christopher D Stephen¹⁴, Anoopum Gupta¹⁴, Chih-Chun Lin¹⁴, S H Subramony¹⁵, Matthew Burns¹⁵, George Wilmot¹⁶, Antoine Duquette¹⁷, Theresa Zesiewicz¹⁸, Marie Y Davis¹⁹, Ali G Hamedani²⁰, Joaquin A Vizcarra²⁰, Stefan M Pulst²¹, Sharon Primeaux²², Christian Rummey²³, Gülin Öz²⁴, Vikram G Shakkottai^#²⁵, Liana S Rosenthal^#²⁶, Sheng-Han Kuo^#^{27

28}; CRC-SCA Consortium

Affiliations

¹ Department of Neurology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA.
² Initiative for Columbia Ataxia and Tremor, Columbia University Irving Medical Center, New York, NY, USA.
³ Taipei Municipal Gan-Dau Hospital, Taipei Veterans General Hospital Branch, Taipei, Taiwan.
⁴ National Ataxia Foundation, Minneapolis, MN, USA.
⁵ Houston Methodist Research Institute, Houston, TX, USA.
⁶ Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁹ Department of Neurology, University of Chicago, Chicago, IL, USA.
¹⁰ Denning Ataxia Center, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
¹² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
¹³ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁴ Ataxia Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Neurology, University of Florida, Gainesville, FL, USA.
¹⁶ Department of Neurology, Emory University, Atlanta, GA, USA.
¹⁷ Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, QC, Canada.
¹⁸ Department of Neurology, University of South Florida, Tampa, FL, USA.
¹⁹ Department of Neurology, University of Washington, Seattle, WA, USA.
²⁰ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²¹ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
²² Department of Neurology, O'Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²³ Clinical Data Science GmbH, Basel, Switzerland.
²⁴ Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, USA.
²⁵ Department of Neurology, O'Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Vikram.Shakkottai@UTSouthwestern.edu.
²⁶ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Liana.Rosenthal@jhmi.edu.
²⁷ Department of Neurology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA. sk3295@cumc.columbia.edu.
²⁸ Initiative for Columbia Ataxia and Tremor, Columbia University Irving Medical Center, New York, NY, USA. sk3295@cumc.columbia.edu.

^# Contributed equally.

PMID: 40679685
DOI: 10.1007/s12311-025-01885-0

Review

The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA)

Yicheng Lin et al. Cerebellum. 2025.

. 2025 Jul 18;24(5):134.

doi: 10.1007/s12311-025-01885-0.

Authors

Affiliations

¹ Department of Neurology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA.
² Initiative for Columbia Ataxia and Tremor, Columbia University Irving Medical Center, New York, NY, USA.
³ Taipei Municipal Gan-Dau Hospital, Taipei Veterans General Hospital Branch, Taipei, Taiwan.
⁴ National Ataxia Foundation, Minneapolis, MN, USA.
⁵ Houston Methodist Research Institute, Houston, TX, USA.
⁶ Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
⁸ Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
⁹ Department of Neurology, University of Chicago, Chicago, IL, USA.
¹⁰ Denning Ataxia Center, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
¹² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
¹³ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁴ Ataxia Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Neurology, University of Florida, Gainesville, FL, USA.
¹⁶ Department of Neurology, Emory University, Atlanta, GA, USA.
¹⁷ Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, QC, Canada.
¹⁸ Department of Neurology, University of South Florida, Tampa, FL, USA.
¹⁹ Department of Neurology, University of Washington, Seattle, WA, USA.
²⁰ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²¹ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
²² Department of Neurology, O'Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²³ Clinical Data Science GmbH, Basel, Switzerland.
²⁴ Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, USA.
²⁵ Department of Neurology, O'Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Vikram.Shakkottai@UTSouthwestern.edu.
²⁶ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Liana.Rosenthal@jhmi.edu.
²⁷ Department of Neurology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA. sk3295@cumc.columbia.edu.
²⁸ Initiative for Columbia Ataxia and Tremor, Columbia University Irving Medical Center, New York, NY, USA. sk3295@cumc.columbia.edu.

^# Contributed equally.

PMID: 40679685
DOI: 10.1007/s12311-025-01885-0

Erratum in

Correction: The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA).
Lin Y, Amokrane N, Worley S, Moore LR, Rosen A, Crespo LP, Trace K, Ashizawa T, Billnitzer A, Perlman S, Fisher A, Bushara K, Geschwind MD, Dietiker C, Gomez CM, Padmanaban M, Opal P, Akhtar RS, Paulson H, Srinivasan S, Ferng A, Ferrari F, Onyike CU, Fishman A, Ying S, Paul A, Schmahmann JD, Stephen CD, Gupta A, Lin CC, Subramony SH, Burns M, Wilmot G, Duquette A, Zesiewicz T, Davis MY, Hamedani AG, Vizcarra JA, Pulst SM, Primeaux S, Rummey C, Öz G, Shakkottai V, Rosenthal LS, Kuo SH. Lin Y, et al. Cerebellum. 2025 Nov 11;24(6):172. doi: 10.1007/s12311-025-01928-6. Cerebellum. 2025. PMID: 41217650 No abstract available.

Abstract

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.

Keywords: Biomarker; Cerebellar ataxias; Natural history study.

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Conflict of interest statement

Declarations. Competing Interests: The authors declare no competing interests.

References

1. Kuo SH. Ataxia. Continuum (Minneap Minn). 2019;25:1036–54. https://doi.org/10.1212/CON.0000000000000753 . - DOI - PubMed
1. Sullivan R, Yau WY, O’Connor E, Houlden H. Spinocerebellar ataxia: an update. J Neurol. 2019;266:533–44. https://doi.org/10.1007/s00415-018-9076-4 . - DOI - PubMed
1. Soong BW, Morrison PJ. Spinocerebellar ataxias. Handb Clin Neurol. 2018;155:143–74. https://doi.org/10.1016/B978-0-444-64189-2.00010-X . - DOI - PubMed
1. Klockgether T, Mariotti C, Paulson HL. Spinocerebellar ataxia. Nat Rev Dis Primers. 2019;5:24. https://doi.org/10.1038/s41572-019-0074-3 . - DOI - PubMed
1. Radmard S, Zesiewicz TA, Kuo SH. Evaluation of cerebellar ataxic patients. Neurol Clin. 2023;41:21–44. https://doi.org/10.1016/j.ncl.2022.05.002 . - DOI - PubMed

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The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA)

Affiliations

The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA)

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources