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Evaluative Clinical Sciences

SRI platforms

Mario Masellis, M.Sc. (Pharm), MD, PhD, FRCPC

Scientist and Professor of Medicine (Neurology)

Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room A4 42
Toronto, ON
M4N 3M5

Phone: 416-480-6100 ext. 689351
Fax: 416-480-5354

For clinical inquiries: Sharon Pierre
Phone: 416-480-6100 ext. 689351
Email: sharon.pierre@sunnybrook.ca

Education:

  • B.Sc., 1994, pharmacology, University of Toronto, Canada
  • M.Sc., 1997, pharmacology, U of T, Canada
  • MD, 2001, medicine, U of T, Canada
  • PhD, 2012, clinical neurosciences, U of T, Canada

Appointments and Affiliations:

  • Scientist, Evaluative Clinical Sciences, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute
  • Professor, Division of Neurology, Department of Medicine, University of Toronto
  • Research Lead, Division of Neurology, Department of Medicine, University of Toronto
  • Clinician-Scientist, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre
  • Consultant Neurologist, Department of Medicine, Sunnybrook
  • Co-director, Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute
  • Director, Cognitive & Movement Disorders Clinic, Department of Medicine, Sunnybrook Health Sciences Centre
  • Chair, Sunnybrook Department of Medicine Association Management Committee

    Research Focus:

    • Neurodegenerative diseases causing dementia and movement disorders, including Parkinson’s / Lewy body spectrum disorders, frontotemporal dementia, Alzheimer’s disease, corticobasal syndrome and progressive supranuclear palsy
    • Early onset genetic forms of dementia
    • Genomics, cognition, biomarkers and neuroimaging

    Research Summary:

    Dr. Mario Masellis obtained his MSc in Pharmacology from the University of Toronto in 1997, completed his medical training at the University of Toronto in 2001 and obtained his board certification (FRCP Canada) in Neurology since 2006. He has completed a clinical research fellowship in Cognitive & Movement Disorders Neurology in 2008 and obtained a PhD in Clinical Neurosciences in 2012.

    His clinical expertise is in the diagnosis and management of both Alzheimer’s and non-Alzheimer’s dementias, including Parkinson’s / Lewy body disorders, frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome.

    His research focuses on how genomic factors impact neuroimaging, biomarker and cognitive phenotypes, as well as response to drugs in neurodegenerative diseases – both sporadic, late-onset and genetic, early-onset subtypes. His work has been published in high impact journals including Brain, JAMA Neurology, Neurology, Lancet Neurology, Journal of Neurology, Neurosurgery and Psychiatry, and Alzheimer’s & Dementia. He was the co-lead of the Ontario Neurodegenerative Disease Research Initiative and he currently co-leads the Theme 2 of the Canadian Consortium on Neurodegeneration in Aging. He serves as a member of the International Parkinson’s and Movement Disorders Society Neuroimaging Study Group, and International Dementia with Lewy Bodies (DLB) Consortium. He is the Canadian national principal investigator of the Genetic Frontotemporal Dementia Initiative (GENFI) and oversees the conduct of this project in Canada. He has received several awards for his work including the Department of Medicine Junior Investigator Award in 2016, the Mid Career Investigator Prize in Research in Aging from the Canadian Institutes of Health Research Institute of Aging in 2021, and the Early Researcher Award from the Ontario Ministry of Research, Innovation, and Science (2012-2017). He has also recently received over 1 million Euros for a Joint Program in Neurodegenerative Disease (JPND) grant as coordinating international investigator. Dr. Masellis has published >300 peer-reviewed articles, with 15,611 total citations, and an h-index of 63 (Scopus).

    Translational Research Program:

    Alzheimer’s disease and related dementias, including Parkinson’s/Lewy body disorders and frontotemporal dementia spectrum disorders, are becoming an epidemic and there is an urgent need to develop disease-modifying therapies to prevent or delay onset. However, clinical trials have failed to find an effective drug or have only shown marginal benefits even though there is evidence of adequate target engagement in many studies, but without a corresponding clinical benefit.

    While there are several reasons for these failures, two of them standout and have been the focus of my ongoing research: 1) the biological processes in the brain underpinning the onset of dementia occur many years before symptom onset so there is a need to develop presymptomatic biomarkers of dementia to identify those at highest risk of converting to dementia and give these drugs early to those ‘at-risk.’ In other words, by the time that dementia symptoms have started, it is too late to reverse the neurodegeneration so we need to understand more about these underlying pathogenic mechanisms and target them early on in their course; and 2) multiple co-pathologies in the brain, including neurodegenerative causes together with cerebrovascular disease, underlie the more common late-onset, sporadic forms of dementia. Thus drugs used in trials targeting a single neuropathological entity, such as Alzheimer’s disease, do not cover the full spectrum of underlying pathology.

    Lack of addressing this complexity may be a key reason why trials of potentially disease-modifying agents have failed since the multiple underlying pathologies in late-onset cases have not been targeted by a cocktail therapeutic approach guided by biomarkers (as done in the cancers). To overcome these challenges, my research focuses on understanding the underlying brain mechanisms of dementia using genomic, brain imaging, cognitive and blood-based biomarkers in two populations: early-onset genetic dementia and late-onset sporadic dementia. I have established a translational research program built on the foundations of precision medicine to address these important challenges, with the ultimate goal of refining clinical trial design to improve therapeutic options available to treat these devastating neurodegenerative diseases.

    Selected Publications:

    See current publications list at PubMed.

    1. Mirza S, Wilkinson T, Masellis M. APOE Genotype and White Matter Hyperintensities in Sporadic Alzheimer Disease. JAMA Neurol. 2024 Jun 1;81(6):662-663. Impact Factor 29 (Trainee publication). Senior Responsible Author.
    2. Pasternak M, Mirza SS, Luciw N, Mutsaerts HJMM, Petr J, Thomas D, Cash D, Bocchetta M, Tartaglia MC, Mitchell SB, Black SE, Freedman M, Tang-Wai D, Rogaeva E, Russell LL, Bouzigues A, van Swieten JC, Jiskoot LC, Seelaar H, Laforce R Jr, Tiraboschi P, Borroni B, Galimberti D, Rowe JB, Graff C, Finger E, Sorbi S, de Mendonça A, Butler C, Gerhard A, Sanchez-Valle R, Moreno F, Synofzik M, Vandenberghe R, Ducharme S, Levin J, Otto M, Santana I, Strafella AP, MacIntosh BJ, Rohrer JD, Masellis M, GENetic Frontotemporal dementia Initiative (GENFI). Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results. Alzheimers Dement. 2024 May 1;20(5):3525-3542. Impact Factor 16.6 (Trainee publication). Senior Responsible Author.
    3. Sanchez E, Wilkinson T, Coughlan G, Mirza S, Baril AA, Ramirez J, Binns MA, Black SE, Borrie M, Dilliott AA, Dixon RA, Dowlatshahi D, Farhan S, Finger E, Fischer CE, Frank A, Freedman M, Goncalves RA, Grimes DA, Hassan A, Hegele RA, Kumar S, Lang AE, Marras C, McLaughlin PM, Orange JB, Pasternak SH, Pollock BG, Rajji TK, Roberts AC, Robinson JF, Rogaeva E, Sahlas DJ, Saposnik G, Strong MJ, Swartz RH, Tang-Wai DF, Tartaglia MC, Troyer AK, Kvartsberg H, Zetterberg H, Munoz DP, ONDRI Investigators, Masellis M. Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative. Alzheimers Dement. 2024 Mar 1;20(3):1753-1770. Impact Factor 16.6 (Trainee publication). Senior Responsible Author.
    4. Medina-Rioja R, Gonzalez-Calderon G, Masellis M. Frontotemporal dementia. CMAJ. 2023 Dec 10;195(48):E1660. Impact Factor 14.6 (Trainee publication). Senior Responsible Author.
    5. Desmarais P, Gao AF, Lanctôt K, Rogaeva E, Ramirez J, Herrmann N, Stuss DT, Black SE, Keith J, Masellis M. White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer’s disease. Alzheimers Res Ther. 2021 Jul 13;13(1):129. PMID: 34256835. Impact Factor 6.116 (Trainee publication). Senior Responsible Author.
    6. Mirza SS, Saeed U, Knight J, Ramirez J, Stuss DT, Keith J, Nestor SM, Yu D, Swardfager W, Rogaeva E, St George Hyslop P, Black SE, Masellis M, Alzheimer’s Disease Neuroimaging Initiative. APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia. Neurology. 2019 Nov 5;93(19):e1807-e1819. PMID: 31575706. Impact Factor 8.055 (Trainee publication). Senior Responsible Author

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