Key areas of focus

  • Rare inherited neurological disorders (including mitochondrial diseases)
  • Neuroinflammation (including Multiple Sclerosis and antibody mediated encephalopathies)
  • Stroke (thromboembolic and haemorhagic, including subarachnoid haemorrhage)
  • Acute brain injury (including Traumatic Brain Injury, TBI, and disorders of consciousness)

The prevalence of neurological disorders is increasing, reflecting advances in the management of acute neurological insults and an ageing population. This leaves many patients with life-long disability that has substantial impact on quality of life, and presents a considerable cost to the NHS.

The over-arching aim of the Neuroscience theme is to use combined expertise in Cambridge to develop new approaches to reduce the impact of neurological disorders across the life course.

Our strategy is to provide core infrastructure underpinning translational neuroscience in four subthemes: (1) Deeply phenotyped patient cohorts; (2) Stratification using state of the art ’omics and imaging; (3) Therapeutic target identification and functional validation; and, (4) Developing new treatments. The infrastructure will underpin externally funded world-leading research programmes in rare and common neurological disorders, and encompass medical and surgical approaches, increasing the pace of discovery of new treatments, and providing a rich training environment for clinicians and allied health care professionals.

The Neuroscience theme is part of the Brain and Mind Health super-theme with Mental Health and Dementia and Neurodegenerative Disease. Together they form a critical mass of expertise for translational research into brain disorders, with a shared infrastructure incorporating clinical informatics, biobanking, deep phenotyping and an experimental medicine platform.

Examples of our work that has had impact on the treatment of neurological diseases:

(1) We were the first to use alemtuzumab in Multiple Sclerosis (MS), including preclinical, early-phase and late-phase clinical trials which led to its licensing (Coles et al, Lancet, 2012a 2012b).  Alumtuzumab works by depleting specific blood cell types (T and B lymphocytes). Following treatment, the restored white blood cell population is much less likely to attack the myelin sheath of nerve cells in the brain and spinal cord, thus arresting MS in its tracks. We led the pivotal clinical trials (Coles et al, Lancet 2013) leading to the market authorisation for alemtuzumab as a treatment for MS (including the UK) and its approval by NICE in 2013, prompting Sir Andrew Dillon to state “Evidence has shown that alemtuzumab is more effective and less expensive than
current similar treatments for those with severe relapsing-remitting multiple sclerosis”. Alemtuzumab has now been licenced in over 40 countries (2016).

(2) Leber hereditary optic neuropathy (LHON) is a common cause of inherited blindness caused by maternally inherited mutations of mitochondrial DNA. The disorder strikes in early adult life, has a major effect on quality of life (Kirkman et al, IOVS 2009), and had no effective treatment (Pfeffer et al, Nature Rev Neurology 2014). Our work characterising the molecular mechanisms and natural history of LHON led to our leadership of a multinational phase IIb randomised placebo-controlled trial (RCT) using idebenone. The RCT (Yu-Wai-Man et al, Brain 2011) and subsequent open-labelled follow-up study (Yu-Wai-Man et al, Brain 2012) underpinned a successful application to the European Medicines Authority to market the drug in Europe, making idebenone the first evidence-based and licensed treatment for a mitochondrial disorder.