RTCure

Rheuma Tolerance for Cure

Summary

Rheumatoid arthritis (RA) occurs when the immune system attacks the joints. Symptoms include painful, swollen joints, stiffness, and fatigue, all of which affect patients’ quality of life. Although RA treatments exist, many patients still struggle to keep their condition under control and many experience unpleasant and sometimes serious side effects of their treatment. Furthermore, there are currently no approved drugs for the early phases of RA.

The RTCure project aims to develop knowledge and tools to aid in the development of treatments for people in the earliest stages of the disease as well as those at risk of developing it. As such, the team will develop and validate new methods to identify people at high risk for RA and tools to monitor the progress of the disease. They will also validate methods to monitor immune tolerance treatments; highly-targeted medicines that stop the immune system’s attacks on the joints while ensuring the immune system remains able to fight off infections.

In the long term, the project hopes that its findings will deliver treatments capable of preventing the disease in those at risk of RA, and curing it in people who are still in the early stages of the disease.

Achievements & News

Scientists identify culprit in organ scarring diseases

An international team of scientists has identified a protein that plays a key role in the organ scarring that is a characteristic of many chronic diseases including idiopathic pulmonary fibrosis (lungs), cirrhosis (liver), kidney fibrosis, systemic sclerosis (the skin), and graft versus host disease (gut). The findings, which suggest new avenues for treatments for these diseases, are published in the journal Nature. ###The study was funded in part by IMI through the RTCure project. Connective tissue cells called fibroblasts help to maintain the integrity of our organs and repair them when they are injured. Usually, once a wound has been healed, the fibroblasts dial down their activity and return to a resting state. However, in diseases such as those listed above, the fibroblasts are over-active, and produce excessive amounts of connective tissue. This results in organ scarring and impairs the ability of the organ to work correctly. In this latest study, researchers studied a protein called PU.1. In normal wound healing, the production of PU.1 is blocked, allowing the fibroblasts to return to a resting state. However, the researchers found that in people with diseases of the connective tissues, PU.1 is activated.

‘PU.1 binds to the DMA and re-programmes the connective tissue cells, resulting in a prolonged deposition of tissue components,’ explained Andreas Ramming of the Friedrich-Alexander-University Erlangen-Nürnberg in Germany, the lead researcher of the study. The team emphasises that PU.1 is not the only factor involved in fibrosis. However, the new findings highlight the central role it plays in the process. Moreover, they showed that deactivating PU.1 causes the fibroblasts to return to their resting state. ‘PU.1 is like the conductor in an orchestra,’ said Dr Ramming. ‘If you take it out, the entire concert will collapse.’ The researchers conclude that drugs to block PU.1 could represent an effective approach to treating a wide range of fibrotic diseases.

RTCure: A novel, preventive approach to treating rheumatoid arthritis

IMI’s RTCure project aims to find ways to prevent and cure rheumatoid arthritis by tackling the autoimmune disease in the very early stages, before debilitating symptoms occur. In an interview with the European Commission’s Research and Innovation Information Centre, scientific coordinator Martina Johannesson at the Karolinska Institutet explains the project’s approach.### ‘Studies of events that precede the development of joint inflammation demonstrate that different molecular mechanisms may be involved in these early phases of the disease. In RTCure, we want to identify and treat the disease as early as possible, before any damage occurs,’ she says. ‘We aim to accomplish this by inhibiting autoimmune responses through treatments that generate immunological tolerance, preventing the immune system from acting against the body’s own cells.’ By studying diverse patients and biomarkers, RTCURE will lay the groundwork for the development and use of different medications based on specific individual disease indicators, enabling targeted and personalised therapy with potential applications in the treatment of other autoimmune diseases in addition to rheumatoid arthritis. ‘The potential impact of RTCURE on the prevention and therapy of rheumatoid arthritis is significant,’ Johannesson says. ‘This treatment approach would prevent many people from developing autoimmune diseases in the first place and enable more effective therapies for current patients, reducing healthcare costs, lost work days and improving quality of life.’

Participants

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EFPIA companies
  • Bristol-Myers Squibb Company Corp, Princeton, NJ, United States
  • Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
  • Janssen Pharmaceutica Nv, Beerse, Belgium
  • Pfizer Limited, Sandwich, Kent , United Kingdom
  • Sanofi-Aventis Deutschland GMBH, Frankfurt / Main, Germany
  • UCB Biopharma, Brussels, Belgium
Universities, research organisations, public bodies, non-profit groups
  • Academisch Ziekenhuis Leiden, Leiden, Netherlands
  • Deutsches Rheuma Forschungszentrumberlin, Berlin, Germany
  • Fondazione Per L'Istituto Di Ricerca In Biomedicina, Bellinzona, Switzerland
  • Karolinska Institutet, Stockholm, Sweden
  • King'S College London, London, United Kingdom
  • Medizinische Universitaet Wien, Vienna, Austria
  • Semmelweis Egyetem, Budapest, Hungary
  • The University Of Birmingham, Birmingham, United Kingdom
  • The University Of Queensland, St Lucia, Australia
  • Universitatsklinikum Erlangen, Erlangen, Germany
  • University Of Glasgow, Glasgow, United Kingdom
  • University Of Newcastle Upon Tyne, Newcastle upon Tyne, United Kingdom
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
  • Anocca AB, Karlskrona, Sweden
  • Apitope International Nv, Diepenbeek, Belgium

Participants
NameEU funding in €
Academisch Ziekenhuis Leiden573 175
Anocca AB138 484
Apitope International Nv169 337
Deutsches Rheuma Forschungszentrumberlin453 450
Fondazione Per L'Istituto Di Ricerca In Biomedicina182 700
Karolinska Institutet1 293 376
King'S College London475 165
Medizinische Universitaet Wien446 725
Semmelweis Egyetem173 700
The University Of Birmingham448 075
The University Of Queensland298 000
Universitatsklinikum Erlangen449 730
University Of Glasgow448 725
University Of Newcastle Upon Tyne449 358
Total Cost6 000 000