Professor Alexandra J. Sinclair MBChB, FRCP, PhD

• 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

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).

Professor Sinclair is the vice chair for the British Association for the Study of Headache (BASH), the UK headache society. She has been a board member of the International Headache Society (IHS) and   European Headache Federation, was on the scientific committee for the North American Neuro-Ophthalmology Society (NANOS) 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.. Professor Sinclair is on the MRC Neuroscience and Mental Health Board and the Midland Neuroscience Teaching and Research Fund Board, as well as the Brain Research UK Scientific Advisory 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 previously led the Complex Headache Service at University Hospital Birmingham. She is a keen advocate and supporter of the multi-disciplinary care approach for Idiopathic intracranial hypertension and traumatic brain injury run 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 Programmes

• MBChB
• BMedSci

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. A previous small clinical trial and shown efficacy for the GLP-1 receptor agonist exenatide to treat idiopathic intracranial Inhypertension. In this research program she will be evaluating the efficacy of a GLP-1 receptor agonist to treat Idiopathic Intracranial Hypertension (IIH) through a large 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 venous sinus stenting compared to cerebrospinal fluid shunting to prevent visual loss in fulminant IIH. The trial is called IIH: Intervention and is a UK wide multicentre-trial.

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. 

Establishing accurate biomarkers for mild traumatic brain injury

Funded by the US Department of Defence and UK Ministry of Defence (total funds > £15.5M)  in collaboration with the Royal Centre of Defence Medicine, this study is seeking to identify accurate reproducible biomarkers in mild traumatic brain injury (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. The study will run over 8 years and is called mTBI Predict.

Investigate the optimal method of therapeutic weight management in IIH

Through a five year research programme funded by the NIHR, a randomised control trial (IIH:WT) has previously evaluated the optimal method of treating IIH through weight loss by comparing a bariatric surgery pathway with a community weight loss intervention, as well as evaluating how much weight loss is needed. 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.

Laboratory science to evaluate mechanism and novel therapeutics in headache and traumatic brain injury

The Translational Brain Science Preclinical Laboratory Team spans from  in vivo to in vitro laboratory research and  aims to understand and treat neurological conditions associated with headache, raised intracranial pressure and traumatic brain injury.

Current Clinical Trials

• IIH-Intervention Trial (CSF shunting vs Venous sinus stenting)
• IIH-Advance Trial (Mounjaro also called Tirzepatide)

Membership of professional bodies

• General Medical Council (4703369)
• Fellow of the Royal College of Physicians (since 2018)
• Member by Distinction of the Faculty of Pharmaceutical Medicine
• Member of the Royal College of Physicians (MRCP) UK (since 2003)
• British Medical Association
• Association of British Neurologists (ABN)
• British Association for the Study of Headache (BASH)

Public engagement

• Previously Patron of charity Idiopathic Intracranial Hypertension (IIH) UK (producing patient information leaflets, information videos and dissemination of clinically relevant information research through the annual patient conference). 

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, Previous Executive Director and Chief Scientific Officer (formed 2018 and listed on the Australian Stock exchange following capital raises of AUS $38).