Professor Sarah J Tabrizi BSc (Hons) MBChB (Hons) FRCP PhD FMedSci graduated in biochemistry, then studied medicine at Edinburgh University where she was awarded the 1992 Leslie Gold Medal for the most distinguished medical graduate. During her time as a trainee neurologist at the National Hospital for Neurology and Neurosurgery (NHNN), Queen Square, Prof Tabrizi worked for Professors Anita Harding and David Marsden, both of whom would make a lasting impression on her.
She undertook an MRC clinical training fellowship PhD studying mitochondrial dysfunction in neurodegeneration with Tony Schapira and Gill Bates from 1996-1999, and it was during this time that she developed a passion for Huntington’s disease (HD) research. Prof Tabrizi obtained a prestigious Department of Health National Clinician Scientist Fellowship at the UCL Queen Square Institute of Neurology in 2002, was promoted to UCL clinical senior lecturer and honorary consultant neurologist in 2003, to reader in 2007 and full professor in 2009.
She is director of the UCL Huntington’s Disease Centre, which she co-founded with Professor Gill Bates in 2016, joint head of the department of neurodegenerative disease at the UCL Queen Square Institute of Neurology, and a principal investigator at the UK Dementia Research Institute at UCL. Since 2003, she has led a highly effective and innovative clinical service for patients and families with Huntington’s disease at the NHNN. Prof Tabrizi leads an internationally recognised research group following two distinct but complementary approaches; basic bench science focusing on cellular mechanisms of neurodegeneration, and an experimental medicine research programme testing innovative therapies to prevent or reverse the neurodegenerative process in HD.
Amongst her early achievements, she identified pathogenic cellular mechanisms in HD and prion biology, a key role for the innate immune system in the pathogenesis of HD, published the first assay of mutant HD protein in human blood cells and CSF, and led two major international multidisciplinary research initiatives, TRACK-HD and Track-On HD. To date, the Track studies have yielded fundamental new insights into the preclinical phase of neurodegeneration in HD including identifying predictors of disease onset, progression, and neurobiological changes occurring twenty years before predicted disease onset, and her team developed new outcome measures now being used in four global HD clinical trials. In 2017, Prof Tabrizi’s team identified a major new genetic modifier of HD progression, MSH3, which led to new drug discovery efforts targeting DNA repair in repeat diseases.
Prof Tabrizi designed, led, and was global PI for the world’s first HTT lowering antisense oligonucleotide (‘gene-silencing’) trial in HD, IONIS-HTTRx. This trial was the first to show successful lowering of the mutant HTT protein in patients, and the first demonstration of antisense-mediated protein suppression in the CNS of patients with a neurodegenerative disease. The results were published in the New England Journal of Medicine in May 2019.
Prof Tabrizi has over 300 peer-reviewed publications to date and her research work has been the subject of articles in NEJM, The Economist, Scientific American, and The Lancet. She has supervised and mentored 28 PhD students to completion. She was elected as a Fellow of the UK Academy of Medical Sciences in 2014. In 2017, she received the seventh Leslie Gehry Brenner Prize for Innovation in Science awarded by the Hereditary Disease Foundation. In 2018, she received the Cotzias Award from the Spanish Society of Neurology, and in 2019 the Yahr Award at the World Congress for Neurology and the Alexander Morison Medal from the Royal College of Physicians of Edinburgh.
Prof Tabrizi receives funding from the Wellcome Trust, UK DRI, CHDI Foundation Inc., the UK Medical Research Council, and the National Institute for Health Research.
More information on Prof Tabrizi and her work can be found on the Huntington’s Disease Centre’s website.
Neurogenetics and neurodegenerative diseases, particularly Huntington’s disease
Scahill RI, Zeun P, Osborne-Crowley K, Johnson EB, Gregory S, Parker C, Lowe J, Nair A, O’Callaghan C,
Langley C, Papoutsi M, McColgan P, Estevez-Fraga C, Fayer K, Wellington H, Rodrigues FB, Byrne LM, Heselgrave A, Hyare H, Sampaio C, Zetterberg H, Zhang H, Wild EJ, Rees G, Robbins TW, Sahakian BJ, Langbehn D, Tabrizi SJ. Biological and Clinical Manifestations of Huntington’s disease in Gene Carriers Very Far from Predicted Onset: The Young Adult Study. The Lancet Neurology. 2020 Jun;19(6):502-512. doi: 10.1016/S1474-4422(20)30143-5. Epub 2020 May 26.
Langbehn D, Stout J, Gregory S, Mills J, Durr A, Leavitt B, Roos R, Long J, Owen G, Johnson H, Borowsky B, Craufurd D, Reilmann R, Landwehrmeyer B, Scahill R, Tabrizi SJ. The effect of polyglutamine CAG repeats on long term progression in Huntington's disease. JAMA Neurology. August 12, 2019. doi:10.1001/jamaneurol.2019.2368
Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, Blair NF, Craufurd D, Priller J, Rickards H, Rosser A, Kordasiewicz HB, Czech C, Swayze EE, Norris DA, Baumann TF, Gerlach I, Schobel SA, Paz E, Smith AV, Bennett CF, Lane RM. Targeting Huntingtin Expression in Patients with Huntington’s Disease. New England Journal of Medicine. 2019 May doi: 10.1056/NEJMoa1900907; included in the NEJM’s Notable Articles of 2019
Flower M, Lomeikaite V, Ciosi M, Cumming S, Morales F, Lo K, Moss D H, Jones L, Holmans P, the TRACK-HD Investigators, the OPTIMISTIC Consortium, Monckton DG, Tabrizi SJ. MSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1. Brain. 2019 Jun 19. pii: awz115. doi: 10.1093/brain/awz115
Goold R, Flower M, Moss DH, Medway C, Wood-Kaczmar A, et al. and Tabrizi SJ. FAN1 modifies Huntington's disease progression by stabilising the expanded HTT CAG repeat. Human Molecular Genetics. 2019 Feb 15;28(4):650-661. [ First description of FAN1 stabilising the CAG repeat in HD.]
Gregory S, Long JD, Klöppel S, Razi A, Scheller E, Minkova L, Johnson EB, Durr A, Roos RAC, Leavitt BR, Mills JA, Stout JC, Scahill RI, Tabrizi SJ*, Rees G. Track-On investigators. Testing a longitudinal compensation model in premanifest Huntington's disease. Brain. 2018 Jul 1;141(7):2156-2166. doi: 10.1093/brain/awy122 * Equal senior author
McColgan P, Gregory S, Seunarine KK, Razi A, Papoutsi M, Johnson E, Durr A, et al. and Rees G, Tabrizi SJ; Brain Regions Showing White Matter Loss in Huntington's Disease Are Enriched for Synaptic and Metabolic Genes. Biological Psychiatry. 2018 Mar 1;83(5):456-465.
Long JD, Mills JA, Leavitt BR, Durr A, Roos RA, Stout JC, Reilmann R, Landwehrmeyer B, Gregory S, Scahill RI, Langbehn DR, Tabrizi SJ; Track-HD and Track-On Investigators. Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis. JAMA Neurology. 2017 Nov 1;74(11):1352-1360. doi: 10.1001/jamaneurol.2017.2107.
Hensman Moss DJ, Pardiñas AF, Langbehn D, Lo K, Leavitt BR, Roos R, et al. Tabrizi SJ. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study. The Lancet Neurology. 2017 Sep;16(9):701-711. Epub 2017 Jun 20. [Awarded the “Insight of the Year” award by the HSG 2017]
Tabrizi SJ, Flower M, Ross C, Wild E. Huntington’s disease – new insights into molecular pathogenesis and therapeutic opportunities. Nature Reviews Neurology. 2020 Oct;16(10):529-546. doi: 10.1038/s41582-020-0389-4. Epub 2020 Aug 14.
Smith AV, Tabrizi SJ. Therapeutic Antisense Targeting of Huntingtin. DNA Cell Biol. 2020 Feb;39(2):154-158. doi: 10.1089/dna.2019.5188. Epub 2019 Dec 10.
Flower MD, Tabrizi SJ. A small molecule kicks repeat expansion into reverse. Nat Genet. 2020 Feb 14. doi: 10.1038/s41588-020-0577-6.
Leavitt BR and Tabrizi SJ. Antisense oligonucleotides for neurodegeneration. Science. 2020 Mar 27;367(6485):1428-1429. doi: 10.1126/science.aba4624.
Tabrizi SJ, Flower M, Ross C, Wild E. Huntington’s disease – new insights into molecular pathogenesis and therapeutic opportunities. Nature Reviews Neurology. 2020 Aug 14. doi: 10.1038/s41582-020-0389-4
Tabrizi SJ, Ghosh R, Leavitt BR. Huntingtin lowering strategies for disease modification in Huntington’s disease. Neuron Journal. 2019 March:101(5):801-819. doi: 10.1016.
Jones L, Houlden H, Tabrizi SJ. DNA repair in the trinucleotide repeat disorders. The Lancet Neurology. 2017 Jan 31;16(1):88-96