Research Studies

Study Title

CRiALS PRESS-ALS (Pre-Symptomatic Studies in ALS)

Enrollment Status

Active-Not Recruiting

Principal Investigators

Michael Benatar, MD, PhD and Joanne Wuu, ScM

Study Type



  • Study the early regional manifestations of ALS


ALS patients, Controls


Click to Expand

Diagnosis of ALS and has at least one region (arm, leg, bulbar) that is unaffected based on clinical examination and EMG
Healthy controls

Study Involvement

Click to Expand

5 study visit (3 months apart) at UMiami over a period of 1 year
Study visits may entail:

  • 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

Click to Expand

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Benatar M, Wuu J, Ravits J. Opportunity and innovation in studying pre-symptomatic amyotrophic lateral sclerosis. Muscle Nerve. 2013 May;47(5):629-31. Epub 2013 Mar 15.

Related Presentations & Lectures

Click to Expand

Benatar M (plenary speaker). Mild Motor Impairment and Prodromal Disease Markers. Platform presentation at the 33rd International Symposium on ALS/MND (Virtual), Dec 6-9, 2022.

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.

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.

Benatar M (keynote speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. The 1st Ontario Clinical ALS Day (OCAD). Toronto, Canada, Oct 21, 2022.

Benatar M (keynote speaker). Progress Towards ALS Prevention. The ALS Association 2022 Virtual Advocacy Conference, June, 2022.

Benatar M (keynote speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. Expert-in-the-Field speaker at the 10th Annual University of California Irvine Health Neuromuscular Colloquium. Irvine, CA, June, 2022.

McHutchison C (presenter), Abrahams S, Cosentino S, Wuu J, Benatar M. Pre-symptomatic mild cognitive and behaviour impairment in ALS-frontotemporal spectrum disorder (ALS-FTSD): A conceptual framework. European Network to Cure ALS (ENCALS) Annual Meeting. Edinburgh, UK, June 1-3, 2022.

Benatar M (invited speaker). Pinpointing Phenoconversion. European Network to Cure ALS (ENCALS) Annual Meeting. Edinburgh, UK, June 1-3, 2022.

Benatar M (invited speaker). Characterizing pre-symptomatic ALS to identify opportunities for early therapeutic intervention. ALS Drug Development Summit. Boston, MA, May 2022.

Benatar M (invited speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. University College London Queen Square Motor Neuron Disease Center Seminar. London, UK, May 2022.

Benatar M (guest speaker). Treatment and Prevention: From Genetic to All ALS. University of Miami Annual ALS Patient Symposium. Virtual, Mar 2022.

Benatar M (invited speaker). Mild Motor Impairment as Prodromal State in ALS. 22nd Annual Packard Center Meeting. Baltimore, MD, Feb/Mar 2022.

Benatar M (invited speaker). Rethinking ALS: Prodrome, Biomarkers, Disease Prevention. Neuroscience Grand Rounds. University of British Columbia, Vancouver, Canada, Feb 2022.

Benatar M (invited speaker). Pre-Symptomatic and Symptomatic Biomarkers for ALS Therapy Development. EverythingALS Community Event. Virtual, Sept 8, 2021.

Benatar M (invited speaker). Pre-Symptomatic ALS: From natural history to early intervention and beyond. International Meeting of Pan-Asian Consortium for Treamtent and Reseach in ALS (PACTALS). Virtual, Sept 17, 2021.

Benatar M (invited speaker). Challenging Dogma and Changing Paradigms in ALS Therapy Development. UCSF Weill Neuroscience Institute Seminar. San Francisco, CA, Sept 2021.

Benatar M (keynote speaker). Pre-symptomatic familial ALS: The long view to disease prevention. University of Pennsylvania Patient Symposium (Fighting for the Future: Education and Support for Familial FTD/ALS). Virtual, Feb 2021.