Along with colleagues, lead for the Musculoskeletal Disease research theme, Professor John Isaacs, has been awarded £1.1m for research into rheumatoid arthritis.
Over the next four years the team will look at tolerogenic dendritic cell therapy for rheumatoid arthritis, as part of the AuToDeCRA 2 project. This work leads on from AuToDeCRA 1, also funded by ARUK, and several interim projects that were supported by the NIHR Newcastle Biomedical Research Centre, which led to the successful funding for the current project.
Clinical need for new arthritis treatment
The immune system is a highly sophisticated ‘army’ of different types of cells. Dendritic cells are the generals of the immune system – co-ordinating and instructing all the other immune cells. During an infection with a flu virus, for example, the dendritic cells are the ones that first recognise that there is danger around and this activates them to instruct some lymphocytes to make antibodies that neutralise the virus and others to directly kill the cells that are harbouring the virus. However, when there is no danger around, an important role for dendritic cells is to keep the rest of the immune system under control so that it doesn’t damage ‘self’ tissues (immune tolerance). In autoimmune diseases such as rheumatoid arthritis immune tolerance goes awry, leading to extensive damage to normal tissues.
Arthritis research in Newcastle
Professor John Isaacs, Professor Catharien Hilkens and their colleagues, have developed a potential treatment for rheumatoid arthritis called autologous tolerogenic dendritic cells. Professor Isaacs comments:
“We generate these from a patient’s white blood cells and, when we inject them back into the patient, they behave like the dendritic cells that keep the immune system at bay. Therefore, with correct ‘programming’, they could switch off the patient’s arthritis; if they are able to do this permanently then they might ultimately provide a cure”.
In previous work (AuToDeCRA 1), the team showed that such cells were safe when injected back into the patient. In AuToDeCRA 2, they will use MRI scans to demonstrate where the cells go once they are injected back. They will also use special immunology tests to measure whether they are indeed reducing the immune system’s ability to attack the joint. Ultimately, this will provide an insight into what happens when the cells are injected in by different routes (into the skin, into a joint and into a lymph node). This will give the best indication in to how best to administer the cells in future trials.
NIHR funding for arthritis research
As lead for the Musculoskeletal Disease theme with the NIHR Newcastle BRC, Professor John Isaacs and colleagues are committed to improving the lives of patients through translational research in arthritis. Following on from the success of AuToDeCRA 1, the NIHR Newcastle Biomedical Research Centre supported two key studies that helped progress the research further in order to discover vital findings that helped support the successful funding from Arthritis Research UK for AuToDeCRA 2.
Dr Catharien Hilkens led the project; ‘Preparing for a phase 2 trial with tolerogenic dendritic cells in rheumatoid arthritis’, which was an optimisation and validation study in preparation for AuToDeCRA 2.
Professor John Isaacs led the study: ‘Identifying response biomarkers in blood and synovium of inflammatory arthritis patients treated with tolerogenic dendritic cells’. This project aimed to investigate biomarkers that would determine whether tolerogenic dendritic cell therapy (tolDC therapy) modulated the immune response by studying a number of factors in synovium and blood. This provided critical data ahead of the next phase that will take place as part of the recently awarded AuToDeCRA 2 project.
As part of the above projects, the NIHR Newcastle BRC also provided supported through clinical trials staff and research nurses who assisted with the recruitment of patients and the treatment necessary for patients to take part in the trials. The NIHR-funded Clinical Research Facility in Newcastle was also a significant support in providing the facilities needed to carry out patient trials.