Research Studies

Study Title

CRiALS Biomarker

Enrollment Status

Recruiting

Principal Investigators

Michael Benatar, MD, PhD and Joanne Wuu, ScM

Study Type

Observational

Goals

Discover and validate a broad range of biomarkers for ALS and related disorders

Enrolling

Patients with ALS (or an ALS related disorder), Controls

Eligibility

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Diagnosis of ALS or a related neurodegenerative disease such as PMA, PLS, HSP, FTD or MSP
Healthy controls

Study Involvement

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The number of study visits may vary, with each visit typically lasting about half a day
Study visits may entail one or more of the following:

  • Family and medical history review
  • Blood, urine, and (optional) CSF collection
  • MRI
  • Neurological exam
  • Neuropsychological assessment
  • Breathing test
  • Fine motor skills testing
  • Surveys/questionnaires

Primary Funding Source

ALS Recover Fund, Kimmelman Estate

Related Publications

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McMillan CT, Wuu J, Rascovsky K, Cosentino S, Grossman M, Elman L, Quinn C, Rosario L, Stark JH, Granit V, Briemberg H, Chenji S, Dionne A, Genge A, Johnston W, Korngut L, Shoesmith C, Zinman L; Canadian ALS Neuroimaging Consortium (CALSNIC), Kalra S, Benatar M. Defining cognitive impairment in amyotrophic lateral sclerosis: an evaluation of empirical approaches. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Mar 7:1-10. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/35253557

Shepheard SR, Karnaros V, Benyamin B, Schultz DW, Dubowsky M, Wuu J, Chataway T, Malaspina A, Benatar M, Rogers ML. Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis. Eur J Neurol. 2022 Apr;29(4):990-999. Epub 2022 Jan 11.

https://pubmed.ncbi.nlm.nih.gov/34967083

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

Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, Jiang N, Kentrup D, Faul C, Alesce L, King PH. FGF23, a novel muscle biomarker detected in the early stages of ALS. Sci Rep. 2021 Jun 8;11(1):12062.

https://pubmed.ncbi.nlm.nih.gov/34103575

Gray E, Thompson AG, Wuu J, Pelt J, Talbot K, Benatar M, Turner MR. CSF chitinases before and after symptom onset in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2020 Aug;7(8):1296-1306. Epub 2020 Jul 14.

https://pubmed.ncbi.nlm.nih.gov/32666680

Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A. Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):538-548. Epub 2019 Aug 21.

https://pubmed.ncbi.nlm.nih.gov/31432691

Gertsman I, Wuu J, McAlonis-Downes M, Ghassemian M, Ling K, Rigo F, Bennett F, Benatar M, Miller TM, Da Cruz S. An endogenous peptide marker differentiates SOD1 stability and facilitates pharmacodynamic monitoring in SOD1 amyotrophic lateral sclerosis. JCI Insight. 2019 May 16;4(10):e122768.

https://pubmed.ncbi.nlm.nih.gov/31092730

Benatar M, Wuu J, Andersen PM, Lombardi V, Malaspina A. Neurofilament light: A candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion. Ann Neurol. 2018 Jul;84(1):130-139. Epub 2018 Aug 16.

https://pubmed.ncbi.nlm.nih.gov/30014505

Gendron TF; C9ORF72 Neurofilament Study Group, Daughrity LM, Heckman MG, Diehl NN, Wuu J, Miller TM, Pastor P, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Benatar M, Silani V, Glass JD, Floeter MK, Jeromin A, Boylan KB, Petrucelli L. Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Ann Neurol. 2017 Jul;82(1):139-146.

https://pubmed.ncbi.nlm.nih.gov/28628244

Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O'Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, Petrucelli L. Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis. Sci Transl Med. 2017 Mar 29;9(383):eaai7866.

https://pubmed.ncbi.nlm.nih.gov/28356511

Shepheard SR, Wuu J, Cardoso M, Wiklendt L, Dinning PG, Chataway T, Schultz D, Benatar M, Rogers ML. Urinary p75(ECD): A prognostic, disease progression, and pharmacodynamic biomarker in ALS. Neurology. 2017 Mar 21;88(12):1137-1143. Epub 2017 Feb 22.

https://pubmed.ncbi.nlm.nih.gov/28228570

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

Foerster BR, Dwamena BA, Petrou M, Carlos RC, Callaghan BC, Churchill CL, Mohamed MA, Bartels C, Benatar M, Bonzano L, Ciccarelli O, Cosottini M, Ellis CM, Ehrenreich H, Filippini N, Ito M, Kalra S, Melhem ER, Pyra T, Roccatagliata L, Senda J, Sobue G, Turner MR, Feldman EL, Pomper MG. Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis. Acad Radiol. 2013 Sep;20(9):1099-106.

https://pubmed.ncbi.nlm.nih.gov/23931423

Benatar M, Wuu J, Fernandez C, Weihl CC, Katzen H, Steele J, Oskarsson B, Taylor JP. Motor neuron involvement in multisystem proteinopathy: implications for ALS. Neurology. 2013 May 14;80(20):1874-80. Epub 2013 May 1.

https://pubmed.ncbi.nlm.nih.gov/23635965

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

Carew JD, Nair G, Andersen PM, Wuu J, Gronka S, Hu X, Benatar M. Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology. 2011 Oct 4;77(14):1370-5. Epub 2011 Sep 21.

https://pubmed.ncbi.nlm.nih.gov/21940617

Carew JD, Nair G, Pineda-Alonso N, Usher S, Hu X, Benatar M. Magnetic resonance spectroscopy of the cervical cord in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011 May;12(3):185-91. Epub 2010 Dec 14.

https://pubmed.ncbi.nlm.nih.gov/21143004

Nair G, Carew JD, Usher S, Lu D, Hu XP, Benatar M. Diffusion tensor imaging reveals regional differences in the cervical spinal cord in amyotrophic lateral sclerosis. Neuroimage. 2010 Nov 1;53(2):576-83. Epub 2010 Jun 28.

https://pubmed.ncbi.nlm.nih.gov/20600964

Metwalli NS, Benatar M, Nair G, Usher S, Hu X, Carew JD. Utility of axial and radial diffusivity from diffusion tensor MRI as markers of neurodegeneration in amyotrophic lateral sclerosis. Brain Res. 2010 Aug 12;1348:156-64. Epub 2010 Jun 1.

https://pubmed.ncbi.nlm.nih.gov/20513367

Related Presentations & Lectures

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Gray E (presenter), AG Thompson, Wuu J, Pelt J, Talbot K, Benatar M, Turner MR. Chitotriosidase level and activity rises in the pre- and early symptomatic phases of ALS. Platform presentation at the 30th International Symposium on ALS/MND, Perth, Australia, Dec 4-6, 2019.

McMillan CT (presenter), Wuu J, Cook P, Olm C, Duda J, Gee J, Clayman CE, Elman L, McCluskey L, Irwin DJ, Grossman M, Benatar M. Baseline and longitudinal volumetric changes associated with presymptomatic C9ORF72 repeat expansion carriers. Platform presentation at the 29th International Symposium on ALS/MND, Glassgow, UK, Dec 7-9, 2018.

Benatar M (presenter), Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A. When does ALS begin? Insights from serum and CSF neurofilament light and heavy. Platform presentation at the 29th International Symposium on ALS/MND, Glassgow, UK, Dec 7-9, 2018.

Benatar M (presenter), Wuu J, Lombardi V, Andersen PM, Malaspina A. Blood and CSF neurofilament levels as biomarkers of pre-symptomatic disease. Platform presentation at the 28th International Symposium on ALS/MND, Boston, MA, Dec 8-10, 2017.

Rogers ML (presenter), Shepheard S, Wuu J, Andersen P, Schultz D, Benatar M. Urinary p75 neurotrophin receptor extracellular domain: A biomarker relevant to ALS therapy development. Platform presentation at the International Symposium on ALS/MND, Boston, MA, Dec 8-10, 2017.

Benatar M (presenter), Reilmann R, Schubert R, Reyes E, Seleski C, Cooley A, Wuu J. Quantitative Motor Testing: Biomarker of Pre-Symptomatic ALS? Platform presentation at the 27th International Symposium on ALS/MND, Dublin, Ireland, Dec 7-9, 2016.

Benatar M (invited speaker). The challenge of early therapeutic intervention in ALS. Invited presentation at the 25th International ALS/MND Meeting. Brussels, Belgium, December 2014.

Nair G, Wuu J, Gronka S, Walker M, Carew J, Benatar M (presenter). MRI evidence of disease in pre-symptomatic SOD1+ individuals at risk for developing familial ALS. Platform presentation at the 22nd International Symposium on ALS/MND, Sydney, Australia, Nov 30 - Dec 2, 2011.

McMillan CT (presenter), Wuu J, Hennessy L, Placek K, Clinical Research in ALS (CRiALS) Study, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Canadian ALS Neuroimaging Consortium (CALSNIC), Quinn C, Elman L, Grossman M, Rampersaud E, Wu G, Taylor JP, Kalra S, Benatar M. Frequency, hazard, and genetic risk factors of cognitive impairment in amyotrophic lateral sclerosis (ALS). Invited presentation at the International Neuropsychological Society Annual Meeting (virtual), Feb 2-5, 2021.

Benatar M (invited speaker). Biomarkers for ALS therapy development. Seminar at the Technical Univeristy of Munich, Germany, Feb, 2021.

Benatar M (invited speaker). Symptomatic and pre-symptomatic biomarkers for ALS therapy development. Johns Hopkins ALS Clinical Trials Unit, Jan, 2021.

Benatar M (invited speaker). ALS Therapy Development. 44th Annual Jerome K Merlis Lectureship in Neuroscience. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, October 2020.

Benatar M (presenter), Wuu J. Conceptual framework and strategies for studying pre-symptomatic ALS. 1st International Pre-Symptomatic ALS Workshop, Miami, FL, Jan 27, 2020.

Benatar M (invited speaker). Biomarkers for ALS Therapy Development. 5th Ottawa International Conference on Neuromuscular Disease and Biology. Ottawa, Canada, October 2019.

Benatar M (invited speaker). ALS Therapy Development: Challenges and Opportunities. Platform presentation at the International Conference on Neuromuscular Disease. Toronto, Canada, July 2016.

Benatar M (invited speaker). Lessons for Charcot-Marie Tooth (CMT) Clinical Trials from ALS Experience. Inherited Neuropathic Consortium Annual Meeting. Miami, FL, January 2016.

Benatar M (invited speaker). Challenges and Opportunities in ALS Therapy Development. Ottawa International Conference on Neuromuscular Biology, Disease and Therapy. Ottawa, Canada, September 2015.

Benatar M (invited speaker). Challenges and Opportunities in ALS Therapy Development. Flinders University Center for Neuroscience Seminar. Adelaide, Australia, September 2015.

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). Challenges and Opportunities in ALS Therapy Development. Congress on Motor and Cognitive Degenerative Diseases. Yachay, Ecuador, January 2015.

Benatar M (invited speaker). ALS Therapy Development: Challenges and Opportunities. ALS Association Wisconsin Chapter. Milwaukee, WI, May 2014.

Benatar M (invited speaker). Pre-Symptomatic Studies in ALS: Rationale, Challenges and Approach. 12th Annual Packard Center Meeting. Baltimore, MD, March 2012.

Benatar M (invited speaker). Pre-fALS: Pre-Symptomatic Studies in ALS. Workshop on Biomarker Studies in Pre-Symptomatic Carriers of Familial ALS/FTD. University of Oxford, Oxford, UK, January 2012.

Benatar M (invited speaker). Identifying Biomarkers in Familial ALS. ALS Association Drug Discovery Meeting. Washington, DC, March 2012.

Benatar M (invited speaker). Piecing Together the Puzzle of ALS: An Emerging Picture. Beijing International Conference on Neurology. Beijing, China, June 2012.

Benatar M (invited speaker). Tackling the Challenges of ALS: A Familial Perspective. 2009 William L. Halseth ALS Visiting Lectureship. University of Colorado School of Medicine, Aurora, CO, February 2010.

Lu D, Rutkove S, Gronka S, Spieker A, Usher S, Wuu J, Andersen P, Benatar M (presenter). Electrical impedance myography (EIM) findings in pre-symptomatic SOD1+ subjects. Platform presentation at the Annual Northeast ALS Consortium Meeting, Washington, DC, Oct 27-29, 2010.

Benatar M (invited speaker). The Limitations of Animal Models of Neurodegenerative Disease. TREAT-NMD/NIH International Conference: Bottlenecks in Translational Medicine in Inherited Neuromuscular Diseases. Brussels, Belgium, November 2009.

Benatar M (invited speaker). Lessons for Huntington’s Disease from Amyotrophic Lateral Sclerosis. World Huntington’s Conference. Vancouver, Canada, September 2009.

Benatar M (invited speaker). Piecing Together the Puzzle of ALS: An Emerging Picture. Visiting Professor and Guest Lecturer, South African Neurological Association Meeting. Johannesburg, South Africa, March 2009.

Benatar M (invited speaker). Strategies for pre-symptomatic biomarker identification in familial ALS. Cold Spring Harbor Symposium on Drug Discovery, Biomarkers, and Clinical Trials for ALS. Banbury Center, Cold Spring Harbor, NY, September 2007.