Professor Alexandra J. Sinclair MBChB, MRCP, PhD

Professor Alex Sinclair

Institute of Metabolism and Systems Research
Professor of Neurology
IMSR Lead for Business Engagement

Contact details

Address
Metabolic Neurology Research Group
Institute of Metabolism and Systems Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Professor Sinclair is Professor of Neurology within the Institute of Metabolism and Systems Research (IMSR) at the University of Birmingham, and Head of the Metabolic Neurology Research Group. She is an international figure in translational research in Idiopathic Intracranial Hypertension (IIH), headache and traumatic brain injury.

Professor Sinclair is a member of the board for the European Headache Federation and is on the scientific committee for the North American Neuro-Ophthalmology Society (NANOS). She is also a council member for the British Association for the Study of Headache (BASH). Professor Sinclair is on the MRC Neuroscience and Mental Health Board and the Midland Neuroscience Teaching and Research Fund Board, as well as being Chair of the Brain Research UK Scientific Advisory Board.

Previously, she was a board member of the International Headache Society (IHS) and was the Deputy Chair for the Association for British Neurologists grouping for Headache and Pain (ABN AAG). She was on the research committee for the Association for British Neurologists and was also the previous patron of the patient charity IIH UK.

Qualifications

  • Fellow of the Royal College of Physicians, 2019
  • PhD, 2010
  • Member of the Royal College of Physicians (MRCP), UK, 2003
  • MBChB, University of Birmingham, 2000

Biography

NASA delegation visits University of Birmingham to discuss its mission to Mars

Professor Sinclair graduated from the University of Birmingham's Medical School in 2000 with honours and attained her MRCP in 2003. She completed her PhD in 2010, funded by a Medical Research Council Clinical Research Training Fellowship. Subsequently, she worked as a National Institute for Health Research (NIHR) Clinical Lecturer in Neurology and then a NIHR funded Clinician Scientist & Neurology Consultant.

She leads a translational research group, which seeks to establish and exploit the pathophysiological mechanisms underpinning the debilitating effects of metabolism and intracranial pressure on headache, traumatic brain injury and Idiopathic Intracranial Hypertension (IIH). She looks to develop therapeutic strategies and generate real impact while improving patient care. The translational portfolio also encompasses a clinical trials programme enabling forward (novel therapeutic molecules are under assessment in patients) and back translation (biomarker evaluation in the laboratory setting). She leads the multidisciplinary Clinical Headache Service and Idiopathic Intracranial Hypertension Service at University Hospitals Birmingham NHS Foundation Trust.

Professor Sinclair is a council member for the British Association for the Study of Headache (BASH). Internationally, she is on the scientific committee for the North American Neuro-Ophthalmology Society (NANOS) and a member of the European Headache Federation Board.

She was previously the Deputy Chair for the Association for British Neurologists grouping for Headache and Pain (ABN AAG) and on the research committee for the Association for British Neurologists. She was also previously a member of the International Headache Society Board.

Professor Sinclair and her research group hosted a high profile visit from NASA, in 2019. NASA are interested in Professor Sinclair's expertise on raised intracranial pressure stemming from her leading Idiopathic Intracranial Hypertension Clinical Service at University Hospitals Birmingham NHS Foundation Trust coupled with her translational science portfolio at the University of Birmingham. Her recent discovery of the novel use of glucogon-like peptide 1 receptor agonists to reduce intracranial pressure are of particular interest to the NASA team in their quest to reduce brain pressure during long duration space travel and allow them to go beyond the moon.

The NASA visitors were: Dr JD Polk, Chief Health and Medical Officer, Dr Terrance Taddeo, Johnson Space Centre Chief Medical Officer, Dr Mike Barratt, Physician and Astronaut, Dr Victor Schneider, Physician Liaison to the NASA Human Research Programme and Dr John Allen, Audiologist and member of the Human Exploration. As part of the visit Dr JD Polk gave a sold-out keynote talk.

Clinical

Professor Sinclair completed her Certificate of Specialist Training in Neurology in 2013 and established and leads the Tertiary Referal Complex Headache Service and multi-disciplinary IIH Service at University Hospital Birmingham. She has a particular interest in traumatic brain injury and post-traumatic headache. She is passionate about driving excellence in clinical care and moving knowledge from research to improved patient outcomes.

Teaching

Teaching Programmes

Research

Professor Sinclair's work is supported by a number of academic grants and collaborations with industry.

Defining new treatment and headache mechanisms in raised intracranial pressure

Through a Sir Jules Thorn Award for Biomedical Science, Professor Sinclair is running a 5-year programme defining new treatment and headache mechanisms in raised intracranial pressure. In particular, she will be evaluating the efficacy of a GLP-1 receptor agonst to treat Idiopathic Intracranial Hypertension (IIH) through a UK randomised control trial. Mechanistic work will comprise human physiology studies with complimentary in vivo studies. 

Establishing the optimal surgical intervention to preserve vision in IIH

This UK multi-centre randomised control trial funded by the NIHR HTA for six years will evaluate the effectiveness and cost effectiveness of dual venus sinus stenting compared to cerebrospinal fluid shunting to prevent visual loss in fulmimant IIH.

Defining the metabolic contributors to intracranial pressure regulation

Utilising in vivo models with intracranial pressure monitoring, the group is exploring mechanisms that regulate intracranial pressure. Some of this work is in collaboration with Professor Rigmor Jensen, University of Copenhagen through a collaborative Lundbeck Foundation grant.

Establishing accurate biomarkers for mild traumatic brain injury

In colloboration with the Royal Centre of Defence Medicine, this project is seeking to identify accurate reproducible biomarkers in mTBI that will predict the most common and disabling consequences of mTBI: primarily persistent post-traumatic headache, as well as cognitive dysfunction, depression, PTSD, dizziness and return to work. This will be achieved through an interdisciplinary harmonised research programme consisting of detailed clinical phenotyping of acute mTBI patients coupled with state-of-the-art multimodal biomarker evaluation (brain imaging, fluid biomarkers, steroid hormones, visual, vestibular, cerebral physiology and EEG biomarkers) in both military and civilian patients.

Investigate the optimal method of therapeutic weight management in IIH

Through a five year research programme funded by the NIHR, a randomised control trial has evaluated the optimal method of treating IIH through weight loss by comparing a bariatric surgery pathway with a community weight loss intervention. The programme additionally seeks to identify the relationship between weight and intracranial pressure and headache. As well as gaining understanding of the mechanisms by which weight loss modifies intracranial pressure.

Other activities

Membership of professional bodies:

Public engagement

Patents and commercialisation

  • Patent: Inventor for the use of GLP-1 agonists in intracranial pressure, no: 1415598 (filed 2014 US, EU, ROW: granted 2019 ROW 2020 EU & US)
  • Orphan Drug designation: European Medicine Agency and FDA 2016.
  • Spin out company: Invex Therapeutics, Founder, Executive Director and Chief Medical Officer (formed 2018 and listed on the Australian Stock exchange following capital raises of AUS $38).

Publications

Recent publications

Article

Burden and Attitude to Resistant and Refractory (BARR) Study Group, Sacco, S, Lampl, C, Maassen Van Den Brink, A, Caponnetto, V, Braschinsky, M, Ducros, A, Little, P, Pozo-Rosich, P, Reuter, U, Ruiz De La Torre, E, Sanchez Del Rio, M, Sinclair, A, Martelletti, P & Katsarava, Z 2021, 'Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance', The Journal of Headache and Pain, vol. 22, 39. https://doi.org/10.1186/s10194-021-01252-4

Galloway, L, Karia, K, White, A, Byrne, M, Sinclair, A, Mollan, S & Tsermoulas, G 2021, 'Cerebrospinal fluid shunting protocol for Idiopathic Intracranial Hypertension improves revision rate', Journal of Neurosurgery.

Elliot, L, Frew, E, Mollan, S, Mitchell, J, Yiangou, A, Alimajstorovic, Z, Ottridge, R, Wakerley, B, Thaller, M, Grech, O, Singhal, R, Tahrani, A, Harrison, M, Sinclair, A & Aguiar, M 2021, 'Cost-effectiveness of bariatric surgery versus community weight management to treat obesity-related idiopathic intracranial hypertension: evidence from a single payer health care system', Surgery for Obesity and Related Diseases, vol. 17, no. 7, pp. P1310-1316. https://doi.org/10.1016/j.soard.2021.03.020

Mollan, S, Mitchell, J, Ottridge, R, Aguiar, M, Alimajstorovic, Z, Cartwright, D, Grech, O, Lavery, G, Westgate, C, Vijay, V, Scotton, W, Wakerley, B, Matthews, T, Ansons, A, Hickman, S, Benzimra, J, Rick, C, Singhal, R, Tahrani, A, Brock, K, Frew, E & Sinclair, A 2021, 'Effectiveness of Bariatric Surgery vs Community Weight Management Intervention for the Treatment of Idiopathic Intracranial Hypertension: A Randomized Clinical Trial', JAMA Neurology, vol. 78, no. 6, pp. 678-686. https://doi.org/10.1001/jamaneurol.2021.0659

Yiangou, A, Mitchell, J, Fisher, C, Edwards, J, Vijay, V, Alimajstorovic, Z, Grech, O, Lavery, G, Mollan, S & Sinclair, A 2021, 'Erenumab for headaches in idiopathic intracranial hypertension: a prospective open-label evaluation', Headache, vol. 61, no. 1, pp. 157-169. https://doi.org/0.1111/head.14026

Pohl, H, Phu Do, T, Garcia-Azorin, D, Hansen, JM, Saxhaug Kristoffersen, E, Nelson, SE, Obermann, M, Sandor, P, Schankin, C, Schytz, HW, Sinclair, A, Schoonman, GG & Gantenbein, AR 2021, 'Green flags and headache: a concept study using the Delphi method', Headache, vol. 2021, no. 00, pp. 1-10. https://doi.org/10.1111/head.14054

Mollan, S, Mytton, J, Tsermoulas, G & Sinclair, A 2021, 'Idiopathic intracranial hypertension: evaluation of admissions and emergency readmissions through the hospital episode statistic dataset between 2002–2020', Life, vol. 11, no. 5, 417. https://doi.org/10.3390/life11050417

Ashina, M, Terwindt, G, Al-Mahdi Al-Karagholi, M, De Boer, I, Lee, MJ, Hay, DL, Schulte, LH, Hadjikhani, N, Sinclair, A, Ashina, H, Schwedt, T & Goadsby, PJ 2021, 'Migraine: disease characterisation, biomarkers, and precision medicine', The Lancet. https://doi.org/10.1016/S0140-6736(20)32162-0

Yiangou, A, Mitchell, J, Nicholls, M, Chong, YJ, Vijay, V, Wakerley, B, Lavery, G, Tahrani, A, Mollan, S & Sinclair, A 2021, 'Obstructive sleep apnoea in women with idiopathic intracranial hypertension: a substudy of the Idiopathic Intracranial Hypertension Weight randomised controlled trial (IIH:WT)', Journal of Neurology.

Mollan, S & Sinclair, A 2021, 'Outcomes measures in idiopathic intracranial hypertension', Expert Review of Neurotherapeutics. https://doi.org/10.1080/14737175.2021.1931127

Review article

Hardy, R, Botfield, H, Markey, K, Mitchell, J, Alimajstorovic, Z, Westgate, C, Sagmeister, M, Fairclough, R, Ottridge, R, Yiangou, A, Storbeck, K-H, Taylor, A, Gilligan, L, Arlt, W, Stewart, P, Tomlinson, J, Mollan, S, Lavery, G & Sinclair, A 2021, '11βHSD1 inhibition with AZD4017 improves lipid profiles and lean muscle mass in Idiopathic intracranial hypertension', Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 1, pp. 174-187. https://doi.org/10.1210/clinem/dgaa766

Mollan, S, Chong, YJ, Grech, O, Sinclair, A & Wakerley, B 2021, 'Current perspectives on idiopathic intracranial hypertension without papilloedema', Life, vol. 11, 472. https://doi.org/10.3390/life11060472

Eigenbrodt, A, Ashina, H, Khan, S, Diener, H-C, Mitsikostas, D, Sinclair, A, Pozo-Rosich, P, Martelletti, P, Ducros, A, Lanteri-Minet, M, Braschinsky, M, Sanchez Del Rio, M, Daniel, O, Ozge, A, Mammadbayli, A, Arons, M, Skorobogatykh, K, Romanenko, V, Terwindt, G, Paemeleire, K, Sacco, S, Reuter, U, Lampl, C, Schytz, HW, Katsarava, Z, Steiner, T & Ashina, M 2021, 'Diagnosis and management of migraine in ten steps: consensus statement', Nature Reviews Neurology. https://doi.org/10.1038/s41582-021-00509-5

Mollan, S, Grech, O & Sinclair, A 2021, 'Headache attributed to idiopathic intracranial hypertension (IIH) and persistent post-IIH headache: a narrative review', Headache. https://doi.org/10.1111/head.14125

Mollan, S, Virdee, J, Bilton, E, Thaller, M, Krishan, A & Sinclair, A 2021, 'Headache for ophthalmologists: current advances in headache understanding and management', Eye. https://doi.org/10.1038/s41433-021-01421-4

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