Research Studies

Study Title

CReATe Consortium: PGB1 (Phenotype-Genotype-Biomarkers) Study

Enrollment Status

Active-Not Recruiting

Principal Investigators

Michael Benatar, MD, PhD

Study Type

Observational

Goals

  • Better understand the phenotype-genotype relationship in ALS and related disorders, as well as the potential impact of environment exposures
  • Develop biomarkers that might be useful in aiding therapy development for this group of disorders

Enrolling

ALS, PMA, PLS, HSP, or MSP patients

Eligibility

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Individuals with a clinical diagnosis of ALS or a related disorder: frontotemporal dementia (FTD), hereditary spastic paraplegia (HSP), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA) or multi-system proteinopathy (MSP).
Selected family members of enrolled affected individuals

Study Involvement

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5 in-person study visits (3-6 months apart), at UMiami (or another study site), over an 18-24-months period
Study visits entail:

  • Family and medical history review
  • Blood, urine, and (optional) CSF collection
  • Neurological exam
  • Neuropsychological assessment
  • Breathing test
  • Questionnaires/surveys

Annual phone calls after last in-person visit

Primary Funding Source

NIH

Related Publications

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Benatar M, Ostrow LW, Lewcock JW, Bennett F, Shefner J, Bowser R, Larkin P, Bruijn L, Wuu J. Biomarker qualification for neurofilament light chain in ALS: theory and practice. Ann Neurol. 2024 Feb;95(2):211-216. Epub 2023 Dec 28.

https://pubmed.ncbi.nlm.nih.gov/38110839

McHutchison CA, Wuu J, McMillan CT, Rademakers R, Statland J, Wu G, Rampersaud E, Myers JR, Hernandez JP, The CReATe Consortium, Abrahams S, Benatar M. The temporal course of cognitive and behavioural changes in motor neuron diseases. J Neurol Neurosurg Psychiatry. 2023 Oct 12:jnnp-2023-331697. Online ahead of print

https://pubmed.ncbi.nlm.nih.gov/37827570

Sattler R, Traynor BJ, Robertson J, Van Den Bosch L, Barmada SJ, Svendsen CN, Disney MD, Gendron TF, Wong PC, Turner MR, Boxer A, Babu S, Benatar M, Kurnellas M, Rohrer JD, Donnelly CJ, Bustos LM, Van Keuren-Jensen K, Dacks PA, Sabbagh MN; Attendees of the inaugural C9ORF72 FTD/ALS Summit. Roadmap for C9ORF72 in frontotemporal dementia and amyotrophic lateral sclerosis: Report on the C9ORF72 FTD/ALS Summit. Neurol Ther. 2023 Dec;12(6):1821-1843. Epub 2023 Oct 17.

https://pubmed.ncbi.nlm.nih.gov/37847372

Varma A, Weinstein J, Seabury J, Rosero S, Zizzi C, Alexandrou D, Wagner E, Dilek N, Heatwole J, Wuu J, Caress J, Bedlack R, Granit V, Statland J, Mehta P, Benatar M, Kaat A, Heatwole C. The amyotrophic lateral sclerosis-health index (ALS-HI): development and evaluation of a novel outcome measure. Amyotroph Lateral Scler Frontotemporal Degener. 2023 May 15:1-9. Online ahead of print

https://pubmed.ncbi.nlm.nih.gov/37190795

Monnakgotla N, Mahungu AC, Heckmann JM, B Gerrit, Mulder N, Wu G, Rampersaud E, Myers J, van Blitterswijk M, Wuu J, Benatar M, Rademakers R, Taylor JP, Nel M. Analysis of structural variants previously associated with ALS in Europeans highlights genomic architectural differences in Africans. Neurol Genet, 2023 Jun 16;9(4):e200077.

https://pubmed.ncbi.nlm.nih.gov/37346932

Zizzi C, Seabury J, Rosero S, Alexandrou D, Wagner E, Weinstein JS, Varma A, Dilek N, Heatwole J, Wuu J, Caress J, Bedlack R, Granit V, Statland JM, Mehta P, Benatar M, Heatwole C. Patient reported impact of symptoms in amyotrophic lateral sclerosis (PRISM-ALS): A national, cross-sectional study. EClinicalMedicine. 2022 Dec 13;55:101768.

https://pubmed.ncbi.nlm.nih.gov/36531982

Wang TW, Wuu J, Cooley A, Yeh TS, Benatar M, Weisskopf M. Occupational lead exposure and survival with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2022 Apr 9:1-8. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/35400246

Nel M, Mahungu AC, Monnakgotla N, Botha GR, Mulder NJ, Wu G, Rampersaud E, van Blitterswijk M, Wuu J, Cooley A, Myers J, Rademakers R, Taylor JP, Benatar M, Heckmann JM. Revealing the mutational spectrum in Southern Africans with amyotrophic lateral sclerosis. Neurol Genet. 2022 Jan 12;8(1):e654. eCollection 2022 Feb.

https://pubmed.ncbi.nlm.nih.gov/35047667

Puentes F, Lombardi V, Lu CH, Yildiz O, Fratta P, Isaacs A, Bobeva Y, Wuu J, ALS Biomarker Consortium, CReATe Consortium, Benatar M, Malaspina A. Humoral response to neurofilaments and dipeptide repeats in ALS progression. Ann Clin Transl Neurol. 2021 Jul 27. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/34318620

Placek K, Benatar M, Wuu J, Rampersaud E, Hennessy L, Van Deerlin VM, Grossman M, Irwin DJ, Elman L, McCluskey L, Quinn C, Granit V, Statland JM, Burns TM, Ravits J, Swenson A, Katz J, Pioro EP, Jackson C, Caress J, So Y, Maiser S, Walk D, Lee EB, Trojanowski JQ, Cook P, Gee J, Sha J, Naj AC, Rademakers R; CReATe Consortium, Chen W, Wu G, Paul Taylor J, McMillan CT. Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis. EMBO Mol Med. 2020 Dec 3:e12595.

https://pubmed.ncbi.nlm.nih.gov/33270986

Benatar M, Zhang L, Wang L, Granit V, Statland J, Barohn R, Swenson A, Ravits J, Jackson C, Burns TM, Trivedi J, Pioro EP, Caress J, Katz J, McCauley JL, Rademakers R, Malaspina A, Ostrow LW, Wuu J; CReATe Consortium. Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology. 2020 Jul 7;95(1):e59-e69. Epub 2020 May 8.

https://pubmed.ncbi.nlm.nih.gov/32385188

Farhan SMK, Howrigan DP, Abbott LE, Klim JR, Topp SD, Byrnes AE, Churchhouse C, Phatnani H, Smith BN, Rampersaud E, Wu G, Wuu J, Shatunov A, Iacoangeli A, Al Khleifat A, Mordes DA, Ghosh S; ALSGENS Consortium; FALS Consortium; Project MinE Consortium; CReATe Consortium, Eggan K, Rademakers R, McCauley JL, Schüle R, Züchner S, Benatar M, Taylor JP, Nalls M, Gotkine M, Shaw PJ, Morrison KE, Al-Chalabi A, Traynor B, Shaw CE, Goldstein DB, Harms MB, Daly MJ, Neale BM. Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein. Nat Neurosci. 2019 Dec;22(12):1966-1974. Epub 2019 Nov 25.

https://pubmed.ncbi.nlm.nih.gov/31768050

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

Pottier C, Rampersaud E, Baker M, Wu G, Wuu J, McCauley JL, Zuchner S, Schule R, Bermudez C, Hussain S, Cooley A, Wallace M, Zhang J, Taylor JP, Benatar M, Rademakers R. Identification of compound heterozygous variants in OPTN in an ALS-FTD patient from the CReATe consortium: a case report. Amyotroph Lateral Scler Frontotemporal Degener. 2018 Aug;19(5-6):469-471. Epub 2018 Mar 20.

https://pubmed.ncbi.nlm.nih.gov/29558868

Related Presentations & Lectures

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McHutchison CA (presenter), Wuu J, Abrahams S, Benatar M. Patterns of longitudinal cognitive and behavioural changes in ALS/MND. ePoster presentation at the 32nd International Symposium on ALS/MND (Virtual), Dec 7-10, 2021.

Statland J (presenter), Karanevich A, Wuu J, Swenson A, Barohn RJ, Schule R, Jackson C, Ravits J, Granit V, McCauley J, Zuckner S, Caress J, Trivedi J, Maiser S, Walk D, Pioro E, McMillan C, Elman L, Katz J, Heckmann J, Burns T, So Y, Wu G, Rampersaud E, Rademakers R, van Blitterswijk M, Taylor JP, Benatar M, on behalf of the CReATe Consortium. Genotype phenotype correlation and longitudinal study of hereditary spastic paraplegia and primary lateral sclerosis. Platform presentation at the 30th International Symposium on ALS/MND, Perth, Australia, Dec 4-6, 2019.

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). Evolving Paradigms in ALS Therapy Development. 147th Annual Meeting of the American Neurological Association. Chicago, IL, Oct 22-25, 2022.

McHutchison C (presenter). Does cognition and behaviour change over time in ALS? Euan MacDonald Centre for MND Research Academic Afternoon. Univeristy of Edinburgh, Edinburgh, UK, June 14, 2021.

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.