Title: The use of PEPITEM and its novel peptido-mimetics for the treatment of autoimmune and chronic inflammatory diseases
Funder: Versus Arthritis

Abstract: Background: Inflammation is a double edged sword. On one hand it is essential for fighting infections and repairing tissues after injury. On the other, prolonged inflammation is associated with immune mediated inflammatory diseases (IMIDs). Thus, treating inflammation is very appealing, a situation recognised for decades. So far efforts in this field have tried to stop the activity of the body’s chemicals that turn on inflammation. As these operate in networks, there is often another agent that can substitute for the one targeted. Therefore, after 30 years of effort there are few really effective anti-inflammatory medicines. We have taken a different approach. When we identified a new pathway that limits inflammation irrespective of how it is initiated, we realised this could be used to treat IMIDs. We have identified a naturally occurring chemical produced by immune cells that could be the basis of a new class of anti-inflammatory medicines. Importantly, our approach means that such medicines could be used in many IMIDS and we have a realistic prospect of delivering new medicines to treat some of the most common and debilitating diseases affecting millions of NHS patients every year. Purpose: We want to use a tool box of novel agents derived from PEPITEM, the immune-regulatory chemical that we recently discovered. These need to be tested so that we know which dose to administer and then tested for their ability to reduce disease in direct comparison to PEPITEM. This will allow us to work out which agent has the best potential as a new medicine. Methodology: Using animal models we will test four new chemical agents based on PEPITEM. Our initial studies will use a rapid test to determine the doses required. Then the agents will be tested in two models of auto-immune disease, rheumatoid arthritis and psoriasis. Exploitation: We hold patents for developing anti-inflammatory medicines from PEPITEM, and this work will help to establish a drug discovery programme based on the leading candidate from our studies. Relevance to the call: This project aligns precisely with the strategic goals of the call: 1. It targets a pathway relevant to multiple IMIDs. 2. Using novel agents based on a new anti-inflammatory pathway ensures an innovative approach. 3. The long term impact of a new medicine based on PEPITEM could be of substantial benefit to patients with IMIDs. 4. A strong patent portfolio and preliminary drug optimisation studies put the project firmly in the translational space. 5. A group of co-applicants with knowledge across a range of diseases and of different stages of translation ensures an integrated approach. 6. There is a strong element of PPI in the development and running of the project. Patient Benefit: We aim to improve the outcome for patients diagnosed with IMIDS, and ultimately help to cure these diseases. This project will support important enabling research for the development of PEPITEM based medicines. This presents a revolutionary opportunity to develop a completely new class of drugs that target, and can potentially cure, a wide range of diseases.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL