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Developing drugs targeting neuroregeneration in stroke

Summary of the impact

Neurons in the central nervous system do not normally regenerate following injury, due in part to the presence of `inhibitory' molecules that actively prevent the growth and/or collateral sprouting of axons. King's College London scientists identified myelin associated glycoprotein (MAG) as the first myelin inhibitory molecule and demonstrated that inhibition of MAG function with a monoclonal antibody promotes axonal regeneration. They have gone on to promote MAG and its receptor (called the NgR1) as druggable therapeutic targets. Their discovery has led the UK's largest pharmaceutical company — GlaxoSmithKline — to develop monoclonal antibodies to MAG and a second myelin inhibitor as clinical drug candidates. The anti-MAG therapeutic successfully completed Phase I and II clinical trials in humans for stroke during 2008-2013.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Neurosciences, Pharmacology and Pharmaceutical Sciences

Establishment of CoCo Therapeutics to take forward new drugs for Alzheimer’s disease

Summary of the impact

Alzheimer's disease (AD) presents society with one of its biggest challenges, yet despite the investment of billions of dollars there are only two classes of drug approved that have minimal benefit in patients. Scientists at King's College London have implicated dysregulation of retinoid signalling as an early feature of the disease and identified the retinoic acid receptor (RAR) family as an attractive drug target. They have gone on to design and patent protect novel orally available RARα selective agonists and demonstrated that they have the potential to restore many of the deficits reported in AD patients. Advent Venture Partners has provided funds to establish a new UK biotechnology company, CoCo Therapeutics Ltd, in partnership with the Wellcome Trust and KCL, to progress this KCL research into the development of a new treatment for AD.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Neurosciences

Identification and validation of nerve growth factor as a peripheral pain mediator

Summary of the impact

There a great need to develop novel drugs to treat pain and in particular chronic pain. Scientists at King's College London (KCL) identified nerve growth factor (NGF) as an important mediator of persistent pain and validated it as a therapeutic target by demonstrating the beneficial effects of neutralising its activity using biological reagents in a number of animal models. The KCL team collaborated closely with the scientists at Genentech who went on to develop a neutralising antibody to NGF for the treatment of pain. This drug has been found to exhibit unprecedented efficacy in phase III trials in man and is currently being considered for registration. Their discovery has also led to several other major pharmaceutical companies initiating drug discovery programs in this area and has contributed to the subject area of pain management.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Neurosciences, Pharmacology and Pharmaceutical Sciences

Excimer laser technology for the correction of refractive disorders

Summary of the impact

Laser eye surgery is one of the most performed and successful types of surgery in the world. King's College London (KCL) researchers have been intimately involved in the development and improvement of techniques for both surgery and after-care to provide optimal results for the tens of millions of patients who undergo this type of treatment. KCL work is used by the world-penetrating companies Zeiss and Avedro to show evidence of the development of their latest techniques such as ReLEx and corneal cross-linking and by guidelines both in the UK (NICE) and abroad (the American Academy of Ophthalmology) to provide information on the long-term benefits and side-effects of laser eye surgery.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Neurosciences, Ophthalmology and Optometry

Retinal rejuvenation therapy

Summary of the impact

Bruch's membrane is a structure in the retina responsible for "waste disposal." Scientists at KCL have provided evidence that matrix metalloproteinase enzymes clear debris from the membrane and that a loss of this activity contributes to a build-up of debris that causes a decline in visual function with normal aging or a more rapid decline in individuals with retinal disease. This has resulted in the development of a highly innovative Retinal Rejuvenation Therapy based on the use of pain-free nanosecond laser pulses to the eye that stimulate a "cleansing" response to improve nutrient supply across, and waste removal from, Bruch's membrane. Clinical studies suggest that this novel treatment has the potential to significantly improve the quality of life of people suffering from age-related macular degeneration and diabetic retinopathy, diseases that cause vision impairment and blindness in millions of people worldwide.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Health

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Ophthalmology and Optometry

14: Preventing heroin overdose deaths with take-home emergency naloxone

Summary of the impact

King's College London (KCL) researchers discovered that heroin overdose is a common and accidental occurrence which is usually witnessed. Risk of fatal overdose on prison release is exceptionally high with 1 in 200 dying of an overdose within four weeks. KCL researchers proposed and tested the acceptability of prior provision of take-home emergency supplies of the heroin antidote naloxone. KCL research created the stimulus for a national training project for families and carers to administer naloxone and as a result, lives are now being saved. KCL research had a substantial impact on national and international policy and service delivery with take-home naloxone programs introduced around the world. KCL researchers lead the first trial to assess the effectiveness of naloxone for prisoners on release.

Submitting Institution

King's College London

Unit of Assessment

Psychology, Psychiatry and Neuroscience

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Public Health and Health Services

Iron Chelators and Hepcidin Analogues for Therapeutic Use

Summary of the impact

Use of the iron chelator drug deferiprone — first developed by researchers at King's College London (KCL) — has extended the lives of thalassaemia patients and is of great utility for those with cardiac problems as it can remove excess iron from the heart. For this reason deferiprone has more recently gained United States approval. KCL researchers have also developed methods for the synthesis and analysis of markers of iron chelation therapy that are being utilised in clinical trials by Novartis Pharmaceuticals and Vifor Pharma and by clinicians. Several neurodegenerative diseases are associated with elevated brain iron levels and the use of deferiprone is also being investigated in clinical trials by ApoPharma and hospitals in the UK and France.

Submitting Institution

King's College London

Unit of Assessment

Allied Health Professions, Dentistry, Nursing and Pharmacy

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Pharmacology and Pharmaceutical Sciences

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