Professor Alexandra J. Sinclair MBChB, MRCP, PhD

Professor Alexandra J. Sinclair

Institute of Metabolism and Systems Research
Professor of Neurology

Contact details

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

Professor Sinclair now works as a Clinician Scientist with a role combining clinical neurology with translational research into idiopathic intracranial hypertension and the neuroendocrine aspects of headache.

Professor Sinclair and her research group recently hosted a high profile visit from NASA. NASA are interested in Professor Sinclair's expertise on raised Intracranial pressure stemming from her leading Idiopathic Intracranial Hypertension clinical service at University Hospital Birmingham 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 key note talk.

Qualifications

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

Biography

Professor Alexandra Sinclair MBChB (Hons) MRCP, PhD graduated from the University of Birmingham School of Medicine in 2000 and attained her MRCP in 2003. She then trained as a Neurology Specialist Registrar in the West Midlands before taking time out of her training to pursue research interests as a Medical Research Council, Clinical Research Training Fellow at the University of Birmingham.

She attained her PhD in 2010 along with a number of prizes for her research: Steven Whittaker Prize, West Midlands Physicians Association (November 2009), Pushpa Chopra Prize, runner-up, Medical Research Society, UK (February 2009), Individual Speciality Award, Medical Research Society, UK (February 2008), Michael Jefferson Prize, Midlands Neurology Society (November 2007) and a poster prize, Society for Endocrinology (March 2007). 

Teaching

Current teaching includes:

  • SP1 student selected teaching module (2nd year MBChB) on “New Treatments in Neurology”
  • Neurology Demonstration Programme (3rd year MBChB)

Research

Alex Sinclair worked as an MRC  Clinical Research Training Fellow (2005 – 2010).  She sought to define 1) an evidence base for treatment and 2) the pathogenesis, of idiopathic intracranial hypertension (IIH).

During the fellowship she conducted a study which provided the first evidence that weight loss is effective at reducing not only headaches and papilloedema, but also intracranial pressure (ICP) in IIH (BMJ 2010;341:c2701). In-vitroand ex-vivostudies addressed the role of obesity and 11B hydroxysteroid dehydrogenase (11B HSD1) a regulator of local cortisol availability, in the regulation of ICP and IIH. She demonstrated expression and activity of 11B HSD1 in the choroid plexus, the cerebrospinal secreting tissue and showed that therapeutic weight loss in IIH was associated with a reduction in global 11β-HSD1 activity, and additionally that the reduction in 11β-HSD1 correlated with weight loss. These studies suggest that elevated 11β-HSD1 may represent a pathogenic mechanism in IIH and inhibition of 11β-HSD1 may have therapeutic potential in IIH.

Alex's current funded research projects include:

  • Sustained treatment of Idiopathic Intracranial Hypertension (IIH) through weight loss induced by bariatric surgery NIHR Clinician Scientist Fellowship
  • Assessing the therapeutic efficacy of an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor (AZD4017) in idiopathic intracranial hypertension (IIH) MRC Mechanisms of Disease grant
  • UK Idiopathic Intracranial Hypertension Clinical Database (GF 010). Healthcare Quality Improvement Partnership (HQIP)
  • Establishing in vitro choroid plexus and arachnoid granulation cell functional model systems of CSF secretion and drainage to further understanding into the pathogenesis’s of Idiopathic intracranial hypertension. Midland Neuroscience Teaching & Research Fund

Other activities

Membership of professional bodies

  • General Medical Council (4703369)
  • 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)

Publications

Mollan SP, Davis B, Silver NC, Shaw S, Malucci C, Wakerley BR, Krishnan A, Chavda S, Ramalingam S, Edwards J, Hemmings K, Williamson M, Burdon MA, Hassan-Smith G, Digre K, Liu GT, Jensen RH, Sinclair AJ (2018) Idiopathic intracranial hypertension: consensus guidelines on management.  JNNP. Jun 14. pii: jnnp-2017-317440

Herd CP, Tomlinson CL, Rick C, Scotton WJ, Edwards J, Ives N, Clarke CE, Sinclair AJ (2018). Botulinum toxins for the prevention of migraine in adults. Cochrane Database of Systematic Reviews (6): CD011616. DOI:10.1002/14651858.CD011616.pub2

Yiangou A, Mitchell J, Markey KA, Scotton W, Nightingale P, Botfield H, Ottridge R, Mollan S, Sinclair AJ (2018). Therapeutic Lumbar Puncture for headache in Idiopathic Intracranial Hypertension: minimal gain, is it worth the pain? Cephalalgia  Jan 1:333102418782192

Scotton W, Mollan S, Walters T, Doughty S, Nightingale P, Botfield H, Markey K, Yiangou A, Williamson S, Sinclair AJ (2018). Characterising the patients experience of diagnostic lumbar puncture in idiopathic intracranial hypertension; a cross-sectional online survey. BMJ Open May 30;8(5):e020445

Scotton W, Botfield H, Uldall M, Westgate C, Mitchell J, Jensen R, Sinclair AJ (2018). Topiramate is as effective as Acetazolamide at lowering intracranial pressure in healthy rodents. Cephalalgia Jan 1:333102418776455

Aojula A, Mollan SP, Horsburgh J, Yiangou A, Markey K, Mitchell J, Scotton W, Keane PA, Sinclair AJ (2018). Segmentation error in spectral domain optical coherence tomography measures of the retinal nerve fibre layer thickness in idiopathic intracranial hypertension. BMC Ophthalmology, Jan 4;17(1):257

Hornby C, Botfield H, O'Reilly MW, Westgate C, Mitchell J, Mollan SP, Manolopoulos K, Tomlinson J, Sinclair AJ (2017). Evaluating the Fat Distribution in Idiopathic Intracranial Hypertension Using Dual-Energy X-ray Absorptiometry Scanning. Neuroophthalmology. Jun 20;42(2):99-104

Botfield HF, Uldall MS, Westgate CSJ, Mitchell JL, Hagen SM, Gonzalez AM, Hodson DJ, Jensen RH, Sinclair AJ (2017) .A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydrocephalus. Sci Transl Med. Aug 23;9(404)

Markey KA, Mollan SP, Jensen RH, Sinclair AJ (2016).  Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions.Lancet Neurol. Jan;15(1):78-91. doi: 10.1016/S1474-4422(15)00298-7

Sinclair AJ, Burdon MA, Nightingale PG, Ball AK, Good P, Matthews TD, Jacks A, Lawden M, Clarke CE, Stewart PM, Walker EA, Tomlinson JW, Rauz S (2010). Low energy diet and intracranial pressure in women with idiopathic intracranial hypertension: prospective cohort study. BMJJul 7;341:c2701

For a full list of Professor Sinclair's publications please see Google Scholar

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