Swine Vesicular Disease

Scientists have grown small blood vessel-like models in the lab and used them to show how damage to the scaffolding that supports these vessels can cause them to leak, leading to conditions such as vascular dementia and stroke. Cambridge scientists have grown small blood vessel-like models in the lab and used them to show how damage to the scaffolding that supports these vessels can cause them to leak, leading to conditions such as vascular dementia and stroke. The study, published today in Stem Cell Reports, also identifies a drug target to 'plug' these leaks and prevent so-called small vessel disease in the brain. Cerebral small vessel disease (SVD) is a leading cause of age-related cognitive decline and contributes to almost half (45%) of dementia cases worldwide. It is also responsible for one in five (20%) ischemic strokes, the most common type of stroke, where a blood clot prevents the flow of blood and oxygen to the brain. The majority of cases of SVD are associated with conditions such as hypertension and type 2 diabetes, and tend to affect people in their middle age. However, there are some rare, inherited forms of the disease that can strike people at a younger age, often in their mid-thirties. Both the inherited and 'spontaneous' forms of the disease share similar characteristics. Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, used cells taken from skin biopsies of patients with one of these rare forms of SVD, which is caused by a mutation in a gene called COL4. By reprogramming the skin cells, they were able to create induced pluripotent stem cells -- cells that have the capacity to develop into almost any type of cell within the body. The team then used these stem cells to generate cells of the brain blood vessels and create a model of the disease that mimics the defects seen in patients' brain vessels. Dr Alessandra Granata from the Department of Clinical Neurosciences at Cambridge, who led the study, said: "Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don't fully understand what damages the blood vessels and causes the disease. Most of what we know about the underlying causes tends to come from animal studies, but they are limited in what they can tell us. "That's why we turned to stem cells to generate cells of the brain blood vessels and create a disease model 'in a dish' that mimics what we see in patients." Our blood vessels are built around a type of scaffolding known as an extracellular matrix, a net-like structure that lines and supports the small blood vessels in the brain. The COL4 gene is important for the health of this matrix. In their disease model, the team found that the extracellular matrix is disrupted, particularly at its so-called 'tight junctions', which 'zip' cells together. This leads to the small blood vessels becoming leaky -- a key characteristic seen in SVD, where blood leaks out of the vessels and into the brain. The researchers identified a class of molecules called metalloproteinases (MMPs) that play a key role in this damage. Ordinarily, MMPs are important for maintaining the extracellular matrix, but if too many of them are produced, they can damage the structure -- similar to how in The Sorcerer's Apprentice, a single broom can help mop the floor, but too many wreak havoc. When the team treated the blood vessels with drugs that inhibit MMPs -- an antibiotic and anti-cancer drug -- they found that these reversed the damage and stopped the leakage. Dr Granata added: "These particular drugs come with potentially significant side effects so wouldn't in themselves be viable to treat small vessel disease. But they show that in theory, targeting MMPs could stop the disease. Our model could be scaled up relatively easily to test the viability of future potential drugs." The study was funded by the Stroke Association, British Heart Foundation and Alzheimer's Society, with support from the NIHR Cambridge Biomedical Research Centre and the European Union's Horizon 2020 Programme.

MULTI-MILLION POUND BOOST FOR RESEARCH PROJECTS AIMED AT DEVELOPING NEW TESTS, TREATMENTS AND DEVICES FOR NEURODEGENERATIVE DISEASES Seven major research projects to receive more than £14 million to develop new tests, treatments and devices for neurodegenerative diseases including Alzheimer’s, motor neuron disease and Parkinson’s disease.The projects receiving the funding include a unique gene therapy for motor neuron disease and a form of dementia, an antibody treatment for Alzheimer’s and testing an anxiety medication to help treat small vessel disease (SVD) to prevent strokes.The grant funding forms part of LifeArc and UK Dementia Research Institute’s strategic £30 million partnership to combine expertise in research and translational science to bridge the gap between laboratory discoveries and clinical applications to accelerate the development of new treatments and therapies. 14 November 2023, London The first projects to be funded through LifeArc’s £30 million strategic partnership with the UK Dementia Research Institute (UKDRI) have been announced today. A total of £14.5 million in grant funding has been allocated to support seven major projects seeking to develop new tests, treatments and medical devices to help the more than 1 million people in the UK living with neurodegenerative conditions including Alzheimer’s disease, motor neuron disease, fronto-temporal dementia (FTD) and Parkinson’s disease. LifeArc’s strategic partnership with UK Dementia Research Institute (UK DRI) was established in 2022 to leverage the strengths of both organisations and advance research in the field of dementia. By combining the research capabilities of UK DRI with LifeArc’s translational expertise the two organisations will aim to bridge the gap between laboratory discoveries and clinical applications to accelerate the development of new treatments and therapies. The projects receiving the funding are: Developing a small molecular drug target to treat amyotrophic lateral sclerosis (ALS and a form of MND) and frontotemporal dementia (FTD), led by Prof Adrian Isaacs (UK DRI at UCL)A low cost highly scalable diagnostic approach for Alzheimer’s, led by Prof Sir David Klenerman (UK DRI at Cambridge)Identifying new combinations of existing drugs to treat motor neuron disease (MND), led by Prof Siddharthan Chandran (UK DRI Director)A unique gene therapy approach for ALS and FTD, led by Dr Marc-David Ruepp (UK DRI at King’s)Repurposing an anti-anxiety drug to treat small vessel disease, led by Prof Paul Matthews (UK DRI at Imperial). Developing an antibody therapy targeting complement, part of the innate immune system for Alzheimer’s, led by Prof Paul Morgan and Dr Wioleta Zelek (UK DRI at Cardiff).Digitally enhanced care for people affected by dementia, led by Prof David Sharp (UK DRI Care Research & Technology). A joint committee between UK DRI and LifeArc agreed the projects and Dr Kay Penicud, UK DRI Director of Innovation & Business, said “It is fantastic to see such a breadth of high-quality translational research from across many of our Centres in these projects. These pioneering projects will bring us ever closer to our mission of new treatments for people affected by dementia. We’re thrilled to be partnering with LifeArc, and excited to see progress in these immensely promising research areas in the coming years.” Dr Karen Skinner, Chief Project & Portfolio Officer at LifeArc said “Our partnership with UK DRI allows us to identify and back the most promising translational research with the potential to transform the lives of those with neurodegenerative conditions. By working together, we reduce risk by further validating opportunities and enhancing appeal to potential future partners, such as pharmaceutical companies, who can subsequently advance these innovations through the clinic and onto the market for those who desperately need them. The initial projects we are funding reaffirm the wealth of untapped research talent that exists within the UK.” Research into neurodegenerative conditions is one of five healthcare themes identified by LifeArc as areas where this is significant unmet patient need. Overall LifeArc is investing up to £100m to tackle neurodegenerative conditions. Find out more about LifeArc and its strategic partnership with UK DRI here. === ENDS === For further press information please contact: Andrew StewartDirector of Communications at LifeArc Andrew.stewart@lifearc.org07970293826 Notes for editors About LifeArc LifeArc is a self-funded, not-for-profit medical research charity. We take science ideas out of the lab and help turn them into medical breakthroughs that can be life-changing for patients. We have been doing this for more than 25 years and our work has resulted in five licensed medicines, including cancer drug pembrolizumab (Keytruda®), lecanemab for Alzheimer’s (Leqembi), and a diagnostic for antibiotic resistance. Our teams are experts in drug and diagnostics discovery, technology transfer, and intellectual property. Our work is in translational science – bridging the gap between academic research and clinical development, providing funding, research and expert knowledge, all with a clear and unwavering commitment to having a positive impact on patient lives. LifeArc is committed to spending £1.3 billion by 2030 in areas of high unmet medical need. LifeArc is a company limited by guarantee (registered in England and Wales under no. 2698321) and a charity (registered in England and Wales under no. 1015243 and in Scotland under no. SC037861). Find out more about our work on www.lifearc.org or follow us on LinkedIn or Twitter. About the UK Dementia Research Institute The national UK Dementia Research Institute (UK DRI) is the single biggest investment in dementia research in the UK. Established in 2017 by its founding funders, the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK, the multi-million-pound Institute is hosted across six leading UK universities: University of Cambridge, Cardiff University, University of Edinburgh, Imperial College London and King’s College London, with its central hub at UCL. The UK DRI works on ways to prevent, treat and care for people with all types of dementia, and ways to keep the brain healthy. www.ukdri.ac.uk

Data from the COMMENCE aortic trial demonstrated low rates of structural valve deterioration (SVD) in the bioprosthetic valves. It represents the longest clinical follow-up for Edwards’ valve with Resliia tissue at a mean of 7.7 years. The company presented data today at the 103rd annual meeting of the American Association for Thoracic Surgery. Resilia, a bovine pericardial tissue treated with anti-calcification technology, serves as the platform for Edwards’ new class of valves. Edwards launched the Sapien 3 valve with Reslia in September 2022. The company is using it while developing the next-generation Sapien X4 valve, which is currently undergoing clinical trials. The build-up of calcium may cause SVD, potentially impacting the long-term durability of bioprosthetic valves. Edwards says. It designed heart valves with Resilia tissue to address the calcification challenges of conventional tissue valves. The company’s Resilia technology could potentially enable valves to last longer. About the Edwards COMMENCE trial Edwards’ COMMENCE trial is a prospective, non-randomized, multi-center, single-arm investigational device exemption study. It evaluated 689 patients across 27 clinical sites in the U.S. and Europe, seeking to demonstrate safety and effectiveness of the valve with Resilia. The patients enrolled at 18 years old and up with diagnosed aortic valve disease, scheduled to undergo aortic valve replacement surgery. Edwards collected long-term follow-up data in a subset and plans to evaluate patients through 10 years. Data from the COMMENCE trial demonstrated low rates of SVD (99.3% freedom from SVD) and clinically stable gradients. It also showed freedom from reoperation — at a 97.2% clip — through seven years. “Edwards Lifesciences is committed to addressing the needs of patients with structural heart disease and our RESILIA tissue technology is designed for enhanced durability, supporting patients’ improved quality of life,” said Larry Wood, Edwards corporate VP and group president, transcatheter aortic valve replacement and surgical structural heart. “The latest COMMENCE aortic trial data emphasizes the value of RESILIA tissue-based offerings in helping patients and their physicians with lifetime management of valve disease.”