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Autoimmune research grants

Connect Immune Research and The Lorna and Yuti Chernajovsky Biomedical Research Foundation have announced the funding of ten new research projects to identify the underlying causes of autoimmune diseases. These 12-month pilot projects will explore how to target pathways common to the development of multiple autoimmune diseases to increase our understanding and generate new treatments. Find out more about the research projects below and read the press release here


Applying functional genomics to identify causal cell states across autoimmune diseases

Lead applicant: Dr Kate Attfield, University of Oxford

Award amount: £99,645

The immune system is a complex network of interacting cell types that are constantly and rapidly changing and reacting to their surroundings, ensuring a robust and rapid response to potential harm. In individuals who are genetically vulnerable, these same processes can also lead to the development of numerous autoimmune diseases, yet how or why this occurs remains unknown.

Using genetic information already generated from thousands of people across multiple autoimmune diseases, this project aims to expose how individual immune cells can be driven to cause disease and how new treatments may be developed to redirect their fate. Specifically, this project focuses on multiple sclerosis and inflammatory bowel disease, using clinical samples from affected tissues and peripheral blood. The identification of cells that are causal (i.e., are actively using regions of their DNA that are associated with disease risk) will be achieved using a broad range of technologies and analytical methods.
Together, these findings aim to contribute to the development of better diagnostic tools and drug design for genetically-associated autoimmune diseases, with a key focus on exclusively eliminating or redirecting only those cells or pathways that are causal.

 

Chimaeric auto-antigen receptor immunotherapy for antiphospholipid syndrome

Lead applicant: Professor Anastasios Karadimitris, Imperial College London

Award amount: £90,000

Antiphospholipid syndrome is an autoimmune condition where the body produces abnormal antibodies called antiphospholipid antibodies that predispose patients to an increased risk of blood clots. This can lead to a number of serious conditions including stroke, heart attack, pulmonary embolism or deep vein thrombosis. Current treatments are limited to long-term anticoagulation medicines that thin the blood rather than therapies that target the disease-causing antiphospholipid antibodies themselves. 

This project aims to precisely identify the immune cells that are the source of the antiphospholipid antibodies in this disease and selectively eliminate them using a new approach called chimaeric auto-antigen receptor (CAAR) immunotherapy. In this one-year project, the team expect to provide in the laboratory proof-of-principle that this approach is feasible and could be effective in treating antiphospholipid syndrome. This would be the first step towards further pre-clinical development of CAAR-T immunotherapy before it is tested in patients with antiphospholipid syndrome in the future.

 

Development of safer ACTH-based drugs for autoimmune diseases

Lead applicant: Dr Trinidad Montero-Melendez, Queen Mary University of London

Award amount: £72,633

Steroids are commonly used to treat autoimmune conditions, such as rheumatoid arthritis, multiple sclerosis and lupus, due to their ability to suppress the immune system. Their use is limited to treat only acute flares of the disease, as they can trigger serious side effects in some people. This can impede their long-term use in chronic conditions which require life-long treatments. 

Adrenocorticotropin hormone (ACTH) is a hormone and is well known for its anti-inflammatory effects. These effects are caused in part due to ACTH’s role in the release of another hormone called cortisol by activating the adrenal glands, and also via activating a separate pathway on immune cells in the inflamed tissues. 

This project aims to build our knowledge of the properties of several new potential anti-inflammatory drugs, whose design is based on adrenocorticotropin (ACTH) hormone. The scientists aim to assess if any of these new drugs have the potential to produce the same effectiveness as current steroid treatments in chronic autoimmune diseases but without the side effects.

 

Intestinal permeability – a new target for autoimmune diseases prevention and therapy

Lead applicant: Professor Claudia Mauri, University College London

Award amount: £100,000 

Autoimmunity occurs when the cells of our own immune system attack our tissues and organs. Although these diseases tend to be studied separately, it is not uncommon that people with one autoimmune disorder develop a second autoimmune disease. This may be partly due to shared genes; however, findings showing that only one of two genetically identical twins may develop autoimmunity challenges this idea. Genetics do not explain the whole story of how autoimmunity is initiated and there must be other environmental triggers for disease. 

This project will establish whether changes in the gut are integral part of several autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and lupus. This project aims to assess whether people living with autoimmunity could benefit from the use of new therapies aimed at restoring balance in the gut. The researchers hope that their findings will change the way that we view organ-specific autoimmune diseases by including the clinical evaluation of gut-markers that are not routinely included in the current management of these diseases.

 

Measuring immunocompetence by assessment of torque teno virus levels in autoimmune diseases following initiation of immunosuppression

Lead applicant: Dr Andreas Kronbichler, University of Cambridge

Award amount: £99,930

Treatments that suppress the immune system are used to control disease activity in autoimmune disorders, but come with the issue that treatments can lead to side effects such as infections. This project aims to characterise a person’s ‘immunocompetence’ and their ability to maintain a functioning immune system capable of responding to and clearing infections, while also having no or minimal autoimmune disease activity. There are currently no markers, either disease characteristics or laboratory tests, to predict a ‘normal immunocompetence’ across different autoimmune disorders. A virus, which is unable to cause any disease, called the torque teno virus has been used in transplant medicine as a marker to predict how well a patient’s immune system is functioning. If the patient has low levels of virus, they are at risk of organ rejection whereas if they have high levels of the virus, they are at risk of falling sick with an infectious disease. This project will test whether this technique can be transferred to monitoring immunocompetence in people with autoimmune conditions. 

This project aims to test the use of torque teno virus as a monitoring tool in two autoimmune diseases – anti-neutrophil cytoplasm antibody-associated vasculitis and systemic lupus erythematosus with a focus on kidney involvement. If levels of torque teno virus in patients proves to be a successful monitoring tool, it could one day help with the care of patients with autoimmune disorders by becoming a part of routine laboratory investigations.

 

Mitochondrial dysfunction as a therapeutic target upstream of interferon type 1 in rheumatic disease

Lead applicant: Dr Meredyth Wilkinson, UCL Great Ormond Street Institute of Child Health

Award amount: £98,719

Juvenile dermatomyositis is a rare autoimmune condition in which the body’s immune system attacks the muscles and skin leading to muscle weakness and skin rashes. Treatments used in juvenile dermatomyositis suppress the body’s immune system. However, these medications do not work for all patients and can cause some unwanted side effects. The researchers have examined genes (the human code) and the pattern of expression of these genes in immune cells from patients with juvenile dermatomyositis. They discovered that genes that code for mitochondria (the ‘powerhouse’ energy producers of the cell) are less active in these patients, even those already on strong treatment, compared with healthy children of the same age. The project will examine this finding in more detail and progress this discovery to look for new and very specific drugs to improve the treatment of juvenile dermatomyositis and other autoimmune conditions such as juvenile systemic lupus erythematous and adult dermatomyositis. If successful, these findings could be rapidly translated to clinical trials since some of the drugs under investigation are already licenced.

 

Neutrophil extracellular traps (NETs) as a therapeutic target for the treatment of autoimmune inflammatory disease

Lead applicant: Dr Helen Wright, University of Liverpool

Award amount: £82,971 

Neutrophils are a type of white blood cell that protect us against infection. However, inappropriate activation of neutrophils, for example in autoimmune diseases such as rheumatoid arthritis and lupus, can cause them to release toxic molecules that they usually use to kill microbes directly onto the surface of our own tissues. This causes damage to small blood vessels in organs such as the kidney and the surface of our joints (cartilage). During certain types of inflammation, neutrophils can dismantle their DNA (genetic code) and release it outside the cell as ‘mesh’ or ‘net’. This is called a neutrophil extracellular trap or NET. NETs are covered in molecules that trap and kill bacteria, and so are an essential process that protects us from infection. However, in autoimmune diseases the NETs can cause the body to mis-recognise some molecules as ‘foreign’, and so create an inappropriate immune response (auto-antibodies) against the tissues that contain high levels of these molecules. We believe that NETs may therefore be a new drug target for treatment of autoimmune inflammatory diseases.  This project will identify key targets for drug development to target NET production in inflammatory diseases, including rheumatoid arthritis and lupus. It is hoped this work will be a step towards increased treatment options and improved disease outcomes for patients with autoimmune diseases.

 

Targeting follicular helper T cells across multiple autoimmune diseases

Lead applicant: Professor Lucy Walker, University College London

Award amount: £99,439 

The common ground between different autoimmune conditions tends to lie early in disease development, when the immune system stops being properly controlled. This ‘loss of immune tolerance’ allows immune responses to develop against our own body, leading ultimately to tissue damage and symptom development. This project aims to nip this process in the bud, by preventing the early interactions between two types of immune cells called T cells and B cells. It may therefore be particularly relevant to people at the early stages of autoimmune disease development, i.e. people who are recently diagnosed, or possibly even people who are at risk of disease development. By targeting the mechanisms that underlie disease development, rather than just the symptoms, this approach may offer a way to stop autoimmune diseases in their tracks. The project brings together two disciplines, immunology and organic chemistry, to develop a novel approach to selectively target follicular helper T cells, a type of immune cell implicated in the development of multiple autoimmune diseases. This could ultimately form the basis for a new therapy for people in the early stages of autoimmune disease development or those at high risk.

 

Targeting pathogenic fibroblasts in immune mediated inflammatory disease

Lead applicant: Professor Adam Croft, University of Birmingham 

Award amount: £99,886

Rheumatoid arthritis and Sjögren's syndrome are both autoimmune diseases where the body’s immune cells attack its own tissues. The researchers have previously identified a subset of a cell type called fibroblasts which seem linked to the disease. It is found in the joints of patients with active rheumatoid arthritis despite treatment, and in patients with active Sjögren's syndrome. These fibroblasts can affect the functioning of the immune system by producing high levels of a protein called fibroblast activation protein-α. The long-term goal of this project is to develop a new strategy to specifically target these fibroblast cells in patients with rheumatoid arthritis and Sjögren's syndrome using a new immunotherapy approach.  If successful, the researchers hope that this will result in a new approach for treating these conditions that leads to long-term reduction of inflammation and prevents joint tissue damage. This will also open the possibility of targeting novel disease pathways in patients who have exhausted currently available treatment options. 

 

The use of PEPITEM and its novel peptide-mimetics for the treatment of autoimmune and chronic inflammatory diseases

Lead applicant: Professor Ed Rainger, University of Birmingham

Award amount: £99,158

The aim of this research is to improve the outcome for patients diagnosed with autoimmune conditions such as rheumatoid arthritis or psoriasis and ultimately help to cure these diseases. Current treatments target the processes that cause the symptoms of autoimmune conditions but fail to effectively cure disease. 

This project’s strategy is to target a pathway, which naturally limits immune cells getting into the tissues in healthy individuals. This pathway doesn’t always function correctly in people with autoimmune diseases, leading to an exaggerated inflammatory response. In the longer-term, the researchers aim to develop a drug based on a molecule called PEPITEM that can restore the function of the pathway in patients. The findings aim to provide a new approach to the clinical management of rheumatoid arthritis, psoriasis and other immune-mediated inflammatory diseases, allowing personalised medicine based on restoring the function of this pathway.