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The cell adhesion molecule N-cadherin has been shown to be required for the survival of cancer cells, their metastasis and the formation of new blood vessels in solid tumours, however, cell adhesion molecules like N-cadherin were generally not considered to be "druggable." Scientists at King's College London have contributed to the development of a "peptide-pipeline" of novel N-cadherin antagonists, including the cyclic HAV peptide (N-Ac-CHAVC-NH2), also now known as Exherin and/or ADH-1, as a "first-in-class" N-cadherin antagonist. This compound was granted FDA organ drug designation for Melanoma in 2008 and successfully completed a number of phase I and II clinical trials, with an additional clinical trial currently recruiting. The demonstration that N-cadherin peptides can be used to treat cancer has changed the perception of what is possible and opened up new clinical and commercial opportunities.
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.
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.
King's College London (KCL) researchers contributed to the discovery that increased C fibre nerve activity in the bladder is a major cause of overactive bladder (OAB) syndrome. Based on this insight, KCL researcher Professor Dasgupta, a surgical urologist at Guy's Hospital, and his team pioneered a new surgical technique for micro-injecting Botulinum Toxin-A (BTX-A) directly into the bladder to suppress C fibres and improve bladder control. The KCL team then conducted the world's first successful clinical trials into the minimally invasive injection of BTX-A n OAB patients. These trials received significant international media coverage. This cost-effective OAB therapy is now licensed by the EU and FDA, is recommended in national and international guidelines, and has significantly improved the treatment of a common health problem.
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.
King's College London (KCL) researchers were the first to identify that an early sign of diabetic kidney disease was the presence of albumin in the urine, a condition known as albuminuria. Building on this finding, the KCL Unit of Metabolic Medicine designed and led in-house, national then international randomised controlled clinical trials with the aim of preserving kidney function in diabetic patients. Ultimately, KCL research established that several drug inhibitors of the renin-angiotensin-aldosterone system (RAAS) can control albuminuria, slow the deterioration of kidney function and significantly extend survival rates in diabetic patients. These drugs are now generically available, and their prescription is recommended by current international clinical guidelines across North America, Europe, Australia and Asia. This shows major impact in terms of reach and significance.
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.
Genetic research at King's College London (KCL) has had significant impact on the current and future care of people with motor neurone disease (MND). KCL researchers discovered several MND-causing genes, which have been taken up by diagnostic and research laboratories throughout the world. This has improved early diagnosis and predictive gene testing in high-risk families and enabled children to be born free of MND by pre-implantation genetic diagnosis. Research laboratories in academia and industry have used mutant genes in cellular and animal models to identify fundamental disease mechanisms and disease-critical pathways to advance drug discovery for this fatal disease.
The use of a formulary to influence prescribing practice is common, with almost all hospitals possessing one that attempts to provide advice on the safe, effective and economic use of medicines. The Maudsley Prescribing Guidelines to Psychiatry steps beyond the function of a mere formulary and provides evidence-based guidance on the use of psychotropic medicines that influences prescribing on both a national and international basis. Now in its 11th Edition and translated into nine languages, much of the evidence in The Guidelines is generated by King's College London research. Additionally, this research is used in other guidelines, in clinical handbooks and in prescribing practices around the world.
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.