Research Studies

Study Title

CRiALS Genetics

Enrollment Status

Current

Principal Investigators

Michael Benatar, MD, PhD and Joanne Wuu, ScM

Study Type

Observational

Goals

Discover genetic causes of ALS and related disorders, as well as modifiers of clinical phenotypes.

Enrolling

Patients with ALS (or an ALS related disorder), Family members

Eligibility

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Diagnosis of ALS or a related neurodegenerative disease such as PMA, PLS, HSP, FTD or MSP
Family members of patients with any of these disorders

Study Involvement

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Screening and eligibility determination (remote)
Blood draw
Genetic testing
Genetic counseling
Medical record review

Primary Funding Source

ALS Recover Fund, Kimmelman Estate

Related Publications

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Benatar M, Wuu J, McHutchison C, Postuma RB, Boeve BF, Petersen R, Ross CA, Rosen H, Arias JJ, Fradette S, McDermott MP, Shefner J, Stanislaw C, Abrahams S, Cosentino S, Andersen PM, Finkel RS, Granit V, Grignon AL, Rohrer JD, McMillan CT, Grossman M, Al-Chalabi A, Turner MR; attendees of the First International Pre-Symptomatic ALS Workshop. Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases. Brain. 2021 Oct 22. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/34677606

Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A; ITALSGEN Consortium, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L; Genomic Translation for ALS Care (GTAC) Consortium, Moreno CAM, Kamalakaran S, Goldstein DB; ALS Sequencing Consortium, Gitler AD, Harris T, Myers RM; NYGC ALS Consortium, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC; Answer ALS Foundation, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E; Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J; SLAGEN Consortium, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Sorarù G, Cereda C; French ALS Consortium, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, et al. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron. 2018 Mar 21;97(6):1268-1283.e6.

https://pubmed.ncbi.nlm.nih.gov/29566793

Nordin A, Akimoto C, Wuolikainen A, Alstermark H, Forsberg K, Baumann P, Pinto S, de Carvalho M, Hübers A, Nordin F, Ludolph AC, Weishaupt JH, Meyer T, Grehl T, Schweikert K, Weber M, Burkhardt C, Neuwirth C, Holmøy T, Morita M, Tysnes OB, Benatar M, Wuu J, Lange DJ, Bisgård C, Asgari N, Tarvainen I, Brännström T, Andersen PM. Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation: a large multinational screening study. Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):256-264. Epub 2016 Dec 12.

https://pubmed.ncbi.nlm.nih.gov/27936955

Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. Epub 2013 Mar 3.

https://pubmed.ncbi.nlm.nih.gov/23455423

Abramzon Y, Johnson JO, Scholz SW, Taylor JP, Brunetti M, Calvo A, Mandrioli J, Benatar M, Mora G, Restagno G, Chiò A, Traynor BJ. Valosin-containing protein (VCP) mutations in sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2012 Sep;33(9):2231.e1-2231.e6. Epub 2012 May 8.

https://pubmed.ncbi.nlm.nih.gov/22572540

Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chiò A, Restagno G, Borghero G, Sabatelli M; ITALSGEN Consortium, Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011 Oct 20;72(2):257-68. Epub 2011 Sep 21.

https://pubmed.ncbi.nlm.nih.gov/21944779

Johnson JO, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin VM, Trojanowski JQ, Gibbs JR, Brunetti M, Gronka S, Wuu J, Ding J, McCluskey L, Martinez-Lage M, Falcone D, Hernandez DG, Arepalli S, Chong S, Schymick JC, Rothstein J, Landi F, Wang YD, Calvo A, Mora G, Sabatelli M, Monsurrò MR, Battistini S, Salvi F, Spataro R, Sola P, Borghero G; ITALSGEN Consortium, Galassi G, Scholz SW, Taylor JP, Restagno G, Chiò A, Traynor BJ. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010 Dec 9;68(5):857-64.

https://pubmed.ncbi.nlm.nih.gov/21145000

Related Presentations & Lectures

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Benatar M (presenter), Fernandez C, Weihl C, Wuu J, Katzen H, Oskarsson B, Steele J, Taylor JP. Motor neuron involvement in multi-system proteinopathy: Implications for ALS/MND. Platform presentation at the 23rd International Symposium on ALS/MND, Chicago, IL, Dec 5-7, 2012.

Benatar M (invited speaker). Genetic Advances in ALS: Insights and Implications. University of Iowa Annual Neurogenetics Meeting. Iowa City, IA, October 2015.

Benatar M (invited speaker). Year in Review: ALS. American Academy of Neurology 65th Annual Meeting. San Diego, CA, March 2013.

Benatar M (invited speaker). Multisystem Proteinopathy: Implications for ALS/MND. Visiting Professor and Guest Lecturer, South African Neurological Association Meeting. Johannesburg, South Africa, March 2009.