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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.
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.
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 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.
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.
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.
Pioneering research led by the University of Aberdeen has directly resulted in the development of an investigational medicinal product for the long-term management and prevention of Alzheimer's disease, breaking new ground in the search for effective Alzheimer's treatments. Although not yet commercially available, this drug has already benefited more than 100 patients and their families. A new spin-out company created to develop the drug has created new jobs and attracted more than US$335 million in investment since 2008. Extensive media coverage of the research has generated increased public awareness of the disease and Aberdeen's cutting-edge research and ability to raise investment. The claimed impact is therefore that a new spin-out company was formed; investments from and collaborations with industry in research and development were generated; and new employment created.
Congenital myasthenic syndromes (CMS) are diseases leading to muscle weakness. They are caused by various gene mutations. However, for many CMS patients with a `limb girdle' pattern of weakness, the gene was unknown, and they were unresponsive to the usual CMS treatments. Research by David Beeson and colleagues has changed this state of affairs. First, they showed that this form of CMS is caused by a mutation in a gene called DOK7. Second, they identified the mechanism by which the mutation causes the disease. Third, they discovered that patients with DOK7 mutations respond to a different class of drug, 03b22 adrenergic receptor agonists. DOK7 mutations are now routinely tested for in clinical practice, and these drugs are standard therapy.
The drug galantamine (Reminyl) received approval for the treatment of early stages of Alzheimer's disease in 2001. However it was not made available on the NHS until March 2011, the effective onset date for the impact. The decision as to whether a treatment is available on the NHS is made by the National Institute of Health and Care Excellence (NICE), who sought additional clinical data and a rationale for the action of the drug. The mechanism of action was elucidated by Lancaster researchers that included chemists and biomedical scientists. These results were part of Alzheimer's Society's campaign to convince NICE to make the drug available on the NHS for early stage Alzheimer's. The resulting impact was direct, enhancing the quality of life for 100,000s of Alzheimer's patients (318,000 galantamine prescriptions were dispensed in the UK in 2012 [8]), with indirect impact on spouses, immediate family, and carers. The impact continues as new patients come into the pool.