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Back view of male patient wearing a performant brainwave scanning headset, adjusted by a female researcher.

About us

Back view of male patient wearing a performant brainwave scanning headset, adjusted by a female researcher.

The Translational Brain Science Research Group, led by Professor Alex Sinclair, conducts pioneering research into idiopathic intracranial hypertension, headache disorders, and the roles of hormones, metabolism, and obesity in neurological disease.

Our translational research programme spans laboratory science, experimental medicine studies, biomarker discovery, and clinical trials, with a strong “bench-to-bedside” approach. Through this work, we aim to advance understanding of disease mechanisms, identify innovative therapeutic strategies, and generate evidence that improves patient care and informs clinical guidelines.

Our Aims

Working with collaborators locally, nationally, and internationally, our group delivers innovative research to advance scientific discovery and generate new insights into conditions that directly impact patient care.

We aim to understand the underlying causes and mechanisms of neurological disease, develop and evaluate new treatments, and translate research findings into improved clinical services and evidence-based care. Through our translational approach, we strive to improve outcomes and quality of life for patients.

We are also committed to training, mentoring, and supporting the next generation of scientists and clinical researchers, helping them develop the skills and experience needed to take the next steps in their careers.

What is Idiopathic Intracranial Hypertension (IIH)?

Idiopathic Intracranial Hypertension (IIH) is a neurological condition characterised by raised intracranial pressure. The condition typically occurs in women with obesity between puberty and menopause. The cause is not fulling understood but our research over the last decade has highlighted that the condition is underpinned by systemic metabolic dysregulation (Yiangou et al Nature Reviews in Neurology 2023). Patients with IIH have swelling of the optic nerve (papilloedema) which can put them at risk of visual loss. Headaches are also a major debilitating features which significantly impact quality of life.

Management and treatment of IIH has been highly variable. The research group has developed evidence to guide how to monitor IIH with optical coherence tomography (OCT), to reduce the need for invasive lumbar punctures to monitor disease, to make informed treatment decisions a how to approach weight management.

Our translational research has explored the role of calcitonin gene-related peptide (CGRP) in headaches associated with IIH through in vivo studies, experimental medicine research, and clinical trials. This work is helping to shape new treatment strategies for IIH-related headaches, including the use of CGRP-targeted therapies and blocking medications.

Current unmet needs include understanding the role of anti-obesity therapies in IIH, as well as the effects of treatment withdrawal on long-term disease management. These questions are being investigated in the IIH Advance trials, which use an innovative and patient-centred trial design aimed at improving accessibility and participation in clinical research.

Whilst most patients with IIH, approximately 93%, can be successfully managed with medical treatment, a small proportion develop severe optic nerve swelling (papilloedema) that threatens vision and requires urgent intervention to rapidly reduce intracranial pressure. Traditionally, cerebrospinal fluid (CSF) shunting procedures have been used in these cases. More recently, venous sinus stenting has emerged as an alternative treatment option and is now performed in many centres worldwide. However, it remains unclear which intervention provides the best short- and long-term visual outcomes, improves headaches, carries the lowest complication rates, and is the most cost-effective. These important questions are being addressed in the NIHR-funded IIH Intervention Trial, which aims to generate high-quality evidence to guide future clinical practice and improve patient care.

Innovative Clinical Trials

Clinical trials are changing, and we are leading the way here at Birmingham. Traditional trials often struggle to recruit patients who truly represent the condition being studied.

Professor Alex Sinclair, Professor of Neurology at the University of Birmingham, is pioneering a decentralised approach for the IIH Pressure Trial, focused on idiopathic intracranial hypertension (IIH) - a debilitating neurological disorder that causes severe headaches and swelling of the optic nerve.

The trial is exploring the potential of GLP‑1 treatments (widely known as “weight‑loss jabs”) to transform outcomes for people living with IIH. Participants can self‑refer via social media, medication is delivered directly to their homes, and follow-up appointments take place via video consultation. Specialist ‘optical coherence tomography’ scans are carried out at local high‑street opticians. Taking clinical trials into the community

Designing clinical trials around patients' lives

Professor Alex Sinclair, Professor of Neurology at the University of Birmingham, is leading a trial for a debilitating neurological condition by recruiting patients directly online, with postal medication, and high-street eye scans, relieving NHS bottlenecks and giving patients control.

Transcript

Professor Alex Sinclair: Currently, it takes a long time to set up clinical trials within the NHS environment, and that's leading to delays in treatments getting to our patients ,but also sometimes it's hard to recruit the patients that are truly representative of the disease that we're trying to treat. And that's because patients are busy, they have jobs, they're looking after their children, and they often can't attend multiple visits at the specialist hospital. So, we're needing to redesign trials to bring them into the community to make them easier for patients to attend.

Professor Dipak Kotecha: So, clinical trials are really core to how we practice medicine, and it's really important if we get enough people involved in clinical trials and we get a broad array of people that are in clinical trials, we can really try to improve how the NHS and other health services can save lives.

So, one of the innovations that we've been trying to do is to use what is already out there. So, if you go and see your General Practitioner, some of your health data is being recorded. What we're trying to do is to reuse that information to help power new clinical trials. 

So, DaRe2THINK is a national system that we've set up in partnership with the MHRA, which is the UK's national regulator, where we've tried to create systems that use this health data and avoid GPs, doctors, and nurses in the community –but also patients –from having to redo things, redo work that's already part of the NHS. So that's what we've developed. And what we have is a system where over 13 million patient records can be reviewed securely and without identifying the individual, but then they can be invited via the General Practitioner or the teams within the NHS to take part in research.

And we've also innovated the whole pipeline so people can take part just by using their mobile phones or their devices. We use the health system to its entirety to make it much easier for NHS patients and their staff to take part in research.

Professor Alex Sinclair: So, we've had to think outside the box to really unburden the NHS and move the trial directly to patients. The trial looks at a group of patients, who are typically women, who are typically of childbearing age and who have obesity, with a condition called idiopathic intracranial hypertension. And we're looking at testing to see if weight loss using the drug Mounjaro, which is a GLP-1medication, will improve their brain pressure and thereby improve their headaches and their vision.

But the trial is quite different. So rather than typically running through the NHS, the patients will be at home. They will self-recruit through social media and advertising through social media. They will then have all of their visits done from home, on a video conference call done by our medical team at the University of Birmingham. They will have their visits done at their local high street optician, where they can monitor their vision. Medication will be posted out to them through an online pharmacy, and then the governance and the safety of the trial will be ensured by still running it through the Birmingham Clinical Trials Unit. So, we've been able to really think about how to make the trial easier to run and how to access those patients who are truly representative of the condition.

Professor Dipak Kotecha: Currently, we have over 500 general practitioners and their staff working across England, and one of the great things is that a quarter of those practices are in the most deprived areas in the country. So here, we're opening up the opportunities for everyone to get involved. Well, we hope that this model of running trials can be taken up in the future so that we can reach underserved communities, and particularly make sure we recruit women into trials, which can be difficult to represent. But ultimately, we want to deliver meaningful clinical research in a more timely way, so we can bring through treatments and discovery science more rapidly, and then we can make meaningful impact on patient care.

Civilians and military to take part in major study to improve concussion prognosis

Professor Sinclair founded and led the mTBI Predict Trial from 2020-2025. This is a long-term study that aims to identify the most accurate, reproducible and clinically practical biomarkers to better identify those at risk of long-term health issues after a head injury. This will be achieved through a harmonised program 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, and cerebral physiology).

Transcript

Professor Alex Sinclair: Head injury is the commonest cause of death and disability in people aged under 40. Mild traumatic brain injury, sometimes called ‘concussion’, accounts for 1.2 million hospital visits each year in the UK. Now, although we call it ‘mild’, it leads to disproportionate impact on future health, and this is echoed by Headway, the brain injury charity. Peter McCabe, the Chief Executive, has added his support, and commented: “We know that even a seemingly minor head injury can have a major impact on a person’s life.”

Now, the consequences of these mild traumatic brain injuries are profound, with 3 in 10 not able to work at 12 months. The long-term effects include: post-traumatic headache, memory disfunction, and poor mental health, with post-traumatic stress disorder in some, as well as balance issues. Returning to work, to sport, to military duty, is not possible in up to a third in the UK. Now there are many causes of traumatic brain injury: road traffic accidents, assault, falls, sports-related head injuries—and, in military personnel (both in peace and even more so during conflict), head injury is common. But identifying those most at risk of these disabling consequences is currently not possible. So, this UK research programme is the first of its kind. We are collaborating closely with our colleagues from the Ministry of Defence.

Air Vice-Marshall Rich Withnall QHS: I am delighted that the Defence Medical Services, including the Defence Medical Rehabilitation Centre at Stanford Hall, will be working hand-in-glove with class-leading civilian colleagues and the National Rehabilitation Centre Programme. I fully support this ground-breaking research, which I am confident will lead to significant clinical innovation to benefit military and civilian patients and have translational positive impact for sporting activities from grassroots to elite levels.

Alex: This programme of work brings together an outstanding multidisciplinary team of researchers from around the UK, coupled with top UK innovation. The study is designed to identify ground-breaking evidence to inform swifter diagnosis, swifter treatment, and enhance long-term management that will benefit across the board, from military personnel to civilians and sports-related brain injury. The study will also have relevance to military veterans with mild traumatic brain injury, by providing indicators of head injury and a focus for future care. Our vision is to identify clinically relevant, practical approaches that can be moved directly into patient care.

  • Long-term impact

    Raised pressure is the brain is also common after a traumatic brain injury, and we are exploring the mechanisms and alterations to the brain which occur after a mild traumatic brain injury and developing prognostic models to determine which patients are more likely to develop long-term disabilities due to persistent headaches, memory disturbances and poor mental health.

University of Birmingham research is set to boost astronaut health for future space missions

Watch the University of Birmingham’s Professor Alex Sinclair and Miss Susan Mollan, of University Hospitals Birmingham NHS Foundation Trust, explain their new study, funded by the UK Space Agency and being done on collaboration with NASA, which is focused on a condition called Space flight-Associated Neuro-ocular Syndrome (SANS), which can have severe consequences for astronauts including blindness.

Transcript

There is an unexpected issue with long duration space flight, astronauts risk losing vision.

My name is Professor Sinclair, I work as a researcher at the Institute of Metabolism and Systems Research at the University of Birmingham, where I run a translational research group looking at brain pressure. I also work as a doctor and neurology consultant where we run one of the largest clinics in the world specialising in brain pressure dynamics.

Space flight neuro-ocular syndrome.

The focus of this project is space flight neuro-ocular syndrome, SANS, and it affects nearly all astronauts who have been in space for greater than three months. This is a major concern because it causes fluid to build up or swelling around the eye nerve, the optic nerve, and also around the brain. Ultimately this can risk visual loss or damage to these structures.

The problem is that we don't have an effective treatment. SANS gets worse the longer the duration of space flight, so this is a real problem when we're trying to think about missions that extend beyond the moon and further out into space.

The project.

Our research project will look at how we can identify really early the signs of SANS, and then monitor this using eye scanning. Then we'll look at how we can treat SANS, and we'll do this using a GLP-1 receptor agonist, which is work developed in our lab designed to help reduce brain pressure, reduce fluid in the brain, reduce fluid around the optic nerve, and therefore protect these structures from damage.

Ultimately, this research project will hope to deliver a new treatment for SANS that will enable safe long-term space exploration to Mars and beyond.

Why is it important.

I want to introduce my colleague and co-investigator, Miss Susan Mollan, who is an ophthalmic consultant at University Hospital Birmingham, and the director of ophthalmic research.

Miss Mollan, why is it important to scan the nerve at the back of the eye for this research project?

Imaging the eye nerve is incredibly important as this can be the first sign of raised intracranial pressure and a condition called papilledema. These specialized scans, OCT, can diagnose this extremely early and also, what our research has shown, can predict brain pressure.

This study is going to benefit astronauts, as we have one of these platforms on the International Space Station, and the astronauts have been performing these scans on themselves, but this is going to help our NHS patients and patients worldwide.

Eye scans with OCT imaging are non-invasive and incredibly quick. So this is the OCT machine. We use it in the NHS to take pictures of the nerve at the back of the eye, it's non-invasive and very, very rapid, and we can get really accurate images on any disease going on in the optic nerve, but it's also available on the International Space Station.

This is a really quick scan because the astronauts have to be able to perform this on themselves whilst in microgravity, so whilst they're floating.

Although we're focusing on a really rare cohort of patients—the astronauts that develop SANS—what we're learning about how to monitor the optic nerve with OCT and what we're learning about how to control the fluid in the optic nerve with GLP-1 receptor agonists is very applicable to our terrestrial patients.

We run a very large clinic at University Hospital Birmingham dealing with a condition called idiopathic intracranial hypertension, which is another condition of fluid on the brain and around the eye nerve. So the things that we're learning with our space research will be very applicable to our patients back on Earth to guide us on how to monitor them more appropriately, and also how to treat them more appropriately.

Professor Alexandra Sinclair and her Translational Brain Science Research Group at the University of Birmingham are collaborating with NASA to advance understanding of Spaceflight Associated Neuro-ocular Syndrome (SANS), a condition caused by prolonged exposure to microgravity that leads to raised intracranial pressure and vision problems in astronauts.

Building on Professor Sinclair’s internationally recognised work in Idiopathic Intracranial Hypertension (IIH), the collaboration compares clinical data from both conditions to better understand how increased brain pressure affects the brain, eye and optic nerve on Earth and in space.

A major focus is the team’s discovery that GLP-1 receptor agonists can reduce intracranial pressure, now progressing through Phase 3 clinical trials. This research has potential to inform new treatments for IIH patients and develop protective countermeasures for astronauts on long-duration missions, including future travel to Mars.

Professor Sinclair and her research group hosted a high profile visit from NASA in 2019 which invited Dr J.D 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 to the University of Birmingham to discuss the novel use of glucogon-like peptide 1 receptor agonists to reduce intracranial pressure

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

Dr Alexandra Sinclair from the University of Birmingham’s Institute of Metabolism and Systems hosted a NASA delegation, including NASA’s Chief Health and Medical Officer, Dr JD Polk, in June 2019. In this video, recorded at the University’s Medical School, Dr Polk discusses the impact of space travel on astronauts’ physiology and research into intracranial hypertension.

The team hosted another visit from NASA in 2026 which invited NASA's Chief Health and Medical Officer, Dr J.D. Polk, alongside clinical and research colleagues focused on managing and treating Space Flight Neuro-ocular Syndrome (SANS) in astronauts. The delegation discussed SANS which is caused by chronic exposure to microgravity and leads to intracranial pressure and optic nerve swelling, resulting in significant visual problems for astronauts and the similarities of Idiopathic Intracranial Hypertension (IIH).

Working with NASA to treat Space Flight Neuro-ocular Syndrome in astronauts

Transcript

Dr J.D. Polk: The reason we're here at University of Birmingham is astronauts get an entity called Spaceflight-Associated Neurocular Syndrome or SANS for short which mimics or looks very similar to idiopathic incraanial hypertension. We've been working with Dr Sinclair and her team for quite some time collaborating on the differences as well as the similarities between those two entities in an effort to find a treatment for SANS. And so in essence it's looking for a treatment for something for astronauts but also making sure that that treatment maybe sheds some light into a disease on the ground. And by comparing notes on both of those we hope to help both populations.

Professor Alex Sinclair: Well, we've done some research in Birmingham which has highlighted a new pathway to reduce brain pressure through reduction of brain fluid production which is cerebral spinal fluid. And we've identified that these medications called GLP-1 receptor agonalists may be able to reduce brain fluid secretion. And we initially showed that in our laboratory research and then moved that through into a Phase 2 clinical trial and are now looking at that in a phase three clinical trial. So I think that was what initially sparked the interest of a potential novel therapeutic that we could translate from our laboratory science into the SANS-population.

We see in our clinical practice that patients with optic nerve edema can develop blind spots and visual loss some of which can be permanent and can be really serious and can lead to blindness in some of our patients. And so it's an area we take very seriously. Not only the monitoring using OCT scanning which I think is done in our clinic but also on the space station to help guide when to treat patients but also knowing how to treat them and to truly think about which is the best medication to use and to think whether these GLP-1 medications would be the right option was something that we got discussions about.

Dr J.D. Polk: For us to further humankind beyond low Earth orbit, um, I'll need a mitigation or a treatment strategy for sands and, uh, this that's why it's so urgent now while the ISS is still active in order to have it when we go to Mars.