“Development and Delivery of novel regulatory T cell immunotherapy in autoimmune liver disease”
Dr Ye Htun Oo, University of Birmingham
Grant award £1,693,848
Funding was awarded to test a potential new therapy for the devastating liver disease, Primary biliary cholangitis (PBC), where the immune system attacks the liver leading to tissue destruction, scarring and eventually liver failure. Currently there is no curative therapy, and patients suffer from disabling symptoms of chronic fatigue and intractable itching. Pre-clinical studies have indicated that regulatory T cells can prevent or reverse autoimmune diseases, and this study will examine whether they may offer a new cellular therapy and could lead to the development of a personalised approach to treating patients.
“Defining Genetic Causes of Cerebral Palsy: A Patient-Centric Approach to Improve Diagnosis and Develop New Treatments”
Dr Manju Kurian, University College London
Grant award £1,494,9434
Dr Manju Kurian and her team will use the award to investigate children diagnosed as having cerebral palsy in whom there is a suspected genetic cause. A variety of investigations will be undertaken to identify these faulty genes and to study how they cause movement difficulties and disability. Specifically, the research will use state of the art techniques to convers patients’ skin cells into brain cells and use this innovative system to test pioneering new treatments that will specifically target the faulty gene, with a view to helping patients previously thought to have an incurable disease.
“Maximizing the health benefits obtained from bariatric surgery”
Professor Rachel Batterham, University College London
Grant award £1,423,625
Research conducted by Professor Batterham’s group suggests that a person’s genetic make-up affects their response to bariatric surgery. It was also found that people with poor weight-loss after surgery have abnormal blood levels of hormones that control appetite compared to people with a good weight-loss. The goal of the work funded by the Trust’s award is to undertake clinical trials to see if the recent findings can be utilised to maximise the health benefit that patients gain from bariatric surgery.
“Myocardial fibrosis and left ventricular decompensation in patients with aortic stenosis”
Dr Mark Dweck, University of Edinburgh
Grant award £1.36 million
The study focuses on patients with the most common form of valve disease, a condition caused by the narrowing of a major valve, which puts heart muscle under pressure and cuts its capacity to pump properly. It can lead to heart failure and sudden death. The research is aimed at enabling doctors to track more effectively when a heart is starting to fail, and to decide the best time to perform surgery with minimum risk to the patient’s overall health. Currently it is difficult to gauge the severity of heart valve disease, particularly in older patients who may also suffer from a number of other health conditions. The timing of corrective surgery is crucial, and if successful this research could lead to a step-change in treatment,
“Stem Cell Therapy for treatment of congenital heart disease: mending the youngest heart”
Professor Massimo Caputo, University of Bristol
This project is aiming for a first in human safety study in infants with complex congenital heart disease, where the long-term outcome remains poor. The lack of growth potential in the materials used currently to repair complex heart disease in young infants is the biggest problem for surgeons. The young patient’s heart outgrows the graft and requires several risky and distressing operations. Professor Caputo and this team will seek a solution to this problem by creating cellular grafts using the patient’s own stem cells, seeded on grafts used in every day surgery.
“Development of interleukin-2 for the treatment of type 1 diabetes”
Dr Frank Waldron-Lynch, University of Cambridge
Grant awarded £903,187
Type 1 diabetes is the most common severe autoimmune disease worldwide, caused by the destruction of insulin producing pancreatic cells. Current treatments with life-long intensive insulin therapy do not produce optimal clinical outcomes, and intensive efforts are being made to develop immune therapies to induce remission of the destructive autoimmunity. Genome-wide studies are now being used to develop new translational strategies to target the key pathways which lead to the loss of immune tolerance, and ultimately to the development of Type 1 diabetes. Pre-clinical studies have shown that the approved drug interleukin-2 (IL-2) can be effective in this context, and the Trust funded a study, which is part of a series aiming to identify whether it is possible to preserve insulin secretion using low dose IL-2. The key aspect of the work was an adaptive clinical trial in patients with Type 1 diabetes, to help determine the optimal dose of IL-2 therapy. The results from the study informed a further trial which it is hoped will test the ultimate goal of whether the dosing regimen established can preserve insulin secretion in newly diagnosed patients
“Bringing next generation sequencing to the next generation: early diagnosis of inherited immune deficiency”
Professor Sophie Hambleton, Newcastle University
Grant awarded £1,495,990
This research focused on the early diagnosis of inherited immune deficiency in children. Using a new DNA sequencing methodology – Whole Genome Sequencing – the programme aimed to develop and test whether this technique performed better than conventional approaches and could benefit children born with a faulty immune system. Pinpointing the causative genes might help predict problems, and aid the selection of the right treatments
“Development of a high throughput discovery programme for druggable pathways in Chron’s disease”
Profession Alison Simmons, University of Oxford
Grant awarded £1,250,000
This research sought to improve understanding of the causes of Crohn’s disease, which is a chronic gastrointestinal inflammatory disease affecting 1 in 1000 people in the UK. Treatment for Crohn’s is relatively ineffective in a significant proportion of patients and the disease places a heavy socio-economic burden on western health care systems.
The work built on earlier studies in the applicants’ laboratories which had identified a number of immunological pathways which are malfunctioning in Crohn’s. The funding enabled the team in Oxford to develop a high throughput platform to test to what extent these immunological pathways are disturbed in the disease. By correlating that information with the patients’ genetic makeup and disease characteristics, the research sought to ascertain whether the data could be used as a prognostic marker or “biomarker” of disease progression. The productive programme paved the way for a clinical trial of novel new compounds to treat inflammatory bowel disease.
“Vascular stem cell therapy for ischaemic retinopathies”
Professor Alan Stitt, Queen’s University Belfast
Grant awarded £697,000
In conditions such as diabetic retinopathy, blood vessels degenerate and fail to supply the retina with the oxygen and nutrition it needs. This can lead to severe visual impairment. Current treatments only address the late stages of the disease and may have serious side effects and there is an urgent need to identify novel treatments which can prevent progression and repair retinal damage. The funding supported research to investigate whether important retinal diseases, looking particularly at ischaemic retinopathies, might be treated effectively with vascular stem cell therapy.
“An international resource for the autozygosity mapping and identification of recessive disease genes in consanguineous families”
Professor Colin Johnson, University of Leeds
Grant awarded £1,134,967
The identification of the genetic basis for recessively-inherited disorders is an important scientific goal, making accurate genetic testing possible, and providing new insights into disease mechanisms, which could lead to new treatments. The team in Leeds had established unique local partnerships for gene-mapping studies, and the Trust’s funding enabled the process for identifying new recessive genes to be expanded considerably, transforming it from what was akin to a “cottage industry” into a rapid, efficient “factory”, with a huge potential for patient benefit.
“Stem cell therapy for liver cirrhosis”
Professor Stuart Forbes, University of Edinburgh
Grant awarded £1,100,000
Mortality from cirrhosis of the liver in the UK has tripled over the last three decades and liver disease is the 5th most common cause of death. The only curative option for end-stage cirrhosis – when it is feasible – is liver transplantation, but donor organ availability cannot meet demand and many patients die waiting for a suitable organ. Those who do receive transplantation require lifelong immunosuppression with the increased health risks this involves. This study funded by the Trust, was targeted at patients who are just below the threshold for liver transplantation. It sought to develop a new approach to the treatment of liver cirrhosis by (a) defining which bone marrow derived stem cells might repair liver damage, (b) defining the mechanisms by which they exert such effects, and (c) using this information to design and implement a phase 1 clinical trial. The funding was transformative for the Forbes laboratory, and facilitated a significant advance in the understanding of the role of bone marrow-derived cells in promoting liver regeneration and resolving fibrosis in the damaged liver.
“Predicting and preventing adolescent depression”
Professor Anita Thapar, Cardiff University
Grant awarded £993,391
Clinical depression is a common, debilitating condition. It is often a chronic, relapsing problem and affected individuals spend a substantial proportion of their total life with depressive symptoms following the onset of illness. Frequently it begins in adolescence, but it is difficult to recognise and treat in this age group. Thus, early recognition of risk and prevention or early intervention are especially important in this group. It is known that children of depressed parents are at especially high risk of developing depression. The over-riding aim of this research was to improve early detection, monitoring, and clinical management of depression in children and adults. The positive results led to the attraction of further funding for follow-up studies.
“Non-invasive detection of disease processes in the CNS through the development of advanced magnetic resonance techniques and a statistical neuro-imaging model of the normal brain”
Professor Andrew Blamire, Newcastle University
Grant awarded £940,054
The aims of this project were to develop magnetic resonance neuroimaging methodology to improve the ability to detect and monitor acute and long-term damage in the brain, and to apply these methods to understand the development of pathological changes in patients with head injury and dementia. The work was very productive and included the most comprehensive imaging investigation to date in mild head injury, which is the largest, but least studied traumatic brain injury.
“Regulatory T cells and the prevention of Type 1 Diabetes”
Professor Colin M Dayan, University of Bristol
Grant awarded £999,754
Building on evidence discovered previously by this group that a particular type of white blood cell (the regulatory T cell) may play a key role in preventing healthy individuals from developing Type 1 diabetes, their focus was on developing new treatments by increasing the number of these T cells. The overall aim of this programme was to develop a novel immunotherapeutic approach to halting the autoimmune process. The results from the study enabled the team to pursue the development of a diabetes peptide “vaccine” in furtherance of that aim.
“Acute infective lung injury: towards cell therapy with anti-protease-transfected monocytes”
Professor John Simpson, University of Edinburgh
Grant awarded £970,021
Ventilator-associated pneumonia commonly caused by superbugs is one of a number of acute lung injuries which have an enormous impact on healthcare. They are commonly fatal, and no effective drug therapy is available. Simpson’s group was interested in developing ways of manipulating the body’s own defence mechanisms by which germs are normally removed. The aim of the Simpson proposal was to develop a gene therapy solution to the problem based on monocytes, which are white blood cells that circulate in the bloodstream but can migrate to areas of infection to assist clearance of germs.
The studies produced a number of significant findings. In particular, in assessing the usefulness of their research approach the group considered it important to examine the biological effects of removing monocytes from the circulation. Their pre-clinical studies found that monocyte depletion produced striking effects by reducing the accumulation of the inflammatory cells, which is characteristic of acute lung injury. The ultimate aim would be to use the results of the study to develop a clinical trial leading to a ground-breaking therapy for this important clinical problem.
“Inflammation in ischaemic brain damage”
Professor Dame Nancy Rothwell, University of Manchester
Grant awarded £995,820
The brain cannot survive without sufficient blood and oxygen. Reduced flow of blood and oxygen (cerebral ischaemia) rapidly causes damage to the brain and may lead to death or severe disability of the patient. This ischaemia occurs during a stroke and is a common secondary response to bleeding in the brain (haemorrhage) and head injury. Limiting the damage caused by ischaemia would benefit many thousands of patients, their careers, and society in general.
The aim of the project therefore was to clarify the cause of ischaemic brain damage with a view to devising a strategy for identifying persons at risk, and for treating stroke victims. The work produced important new findings which helped pave the way eventually for a phase 3 clinical trial.
“Gene therapy for X-linked retinitis pigmentosa (X_LRP)”
Professor Robin Ali and Professor Adrian Thrasher, The Institute of Ophthalmology and Institute of Child Health at University College London
Grant awarded £993,138
The hypothesis was that gene therapy offered a potential new way to treat inherited eye disease in young people. The Trust’s grant funded a 5-year programme of research which would enable the investigators to obtain convincing data and to develop the technologies necessary to make a clinical trial possible.
The results were hugely encouraging. So much so that the UCL team was able to use the findings to help obtain a substantial new grant from the Department of Health to conduct the first clinical trial of gene therapy for the treatment of a particular form of childhood blindness caused by a gene abnormality which prevents normal function of the retina. Having established the proof of principle, the work paves the way for the development of gene therapy approaches for a broad range of eye disorders.