Biomedical Research Centre at the Kennedy Institute

Diseases are traditionally managed within specific medical specialities, which often relate to parts of the body: rheumatology, dermatology, gastroenterology and so on. However, patients with disease in one organ often experience similar problems in another, suggesting a more holistic cross disease approach may be more effective. A patient with rheumatoid arthritis, for example, may have to visit a number of medical specialists as they have symptoms in many organs.

Immune Mediated Inflammatory Diseases (IMIDs) are a common and growing problem for the NHS. They are often treated in very similar ways (combination therapy) with very similar drugs (steroids and anti-TNF biologics). This has led the patient partner groups to ask: if these diseases share so much in common, why are they not investigated in a common manner?

Through initiatives like the Human Cell Atlas, it is known that some types of cells are found across all organs, while others are specific to an organ. The aim of the inflammation across tissues theme is to identify a common set of cells that would allow inflammation to be targeted across all organs; as well as those cells that are unique to each organ.

The theme will testing the hypothesis that unravelling the common cellular and molecular basis of inflammation across four distinct but clinically related tissues in children and adults will lead to a new tissue-based, cellular understanding of inflammation. This will:

• Allow 'basket trials' over a range of IMIDs, where a drug is tested against two or more diseases.
• Link the cellular processes that underpin different diseases to new or repurposed drugs
• Enable research studies to assess quickly how effective drugs are in tackling different diseases.
• Advance the concept of 'precision pathology' – using the right drug for the right IMID at the right dose.

SUB THEMES

CLINICAL COHORTS

Both paediatric and adult, in oxford and other UK centres – across seven diseases that reflect the full spectrum of autoimmune and auto inflammatory disease, covering a number of organs (skin, gut, joints, liver).

It includes the Arthritis Therapy Acceleration Programme (A-TAP), the True Colours online tool that has allowed large cohorts of people with ulcerative colitis to manage their own condition.

GENES, MICROBIOME AND INFORMATICS

Using genetic research to diagnose and predict IMIDs that are caused by variations in a single gene (Monogenic disorders).

Key elements will be the Paediatric Inflammatory Bowel Disease (PIBD) BioResource aimed at investigating inflammatory bowel disease (IBD) in children, and the Inflammatory Arthritis Microbiome Consortium, which aims to manipulate microorganisms in the gut to treat inflammatory arthritis.

TISSUE BIOLOGY

Concerns the collection, transport, storage and processing of IMID tissue samples – vital for validating our approaches, and building on processes as part of the A-TAP partnership.

This includes the Cartography consortium, a major industry-academic collaboration with Janssen to develop a cellular map of the genes and proteins implicated across a range of IMIDs, with a view to better understanding how the disease works and so treat the right patients with the right medications – and inform the development of new therapies.

CLINICAL TRIALS

Clinical trials the aim to identify new drug therapies for a range of inflammatory conditions using innovative trial designs. A new Inflammation and Advanced Cellular Therapy (I-ACT) trials team has been set up to carry out early-phase experimental clinical trials in collaboration with Oxford Experimental Medicine Research Facility.