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Testing a cancer drug for arthritis

Scientists at Newcastle University have been awarded £1m for a clinical trial to see whether a drug developed to treat cancer can be ‘repurposed’ to treat rheumatoid arthritis.

Funded by the Medical Research Council and aimed at treating patients who do not respond to existing treatments, the award has been announced by the Universities and Science Minister David Willetts.

It is one of the innovative business and academic projects from across the UK’s health sector which will benefit from a new £93.2 million package of support announced today.

The drug works by targeting a different type of cell from conventional therapies and could therefore succeed where conventional treatments have failed. The drug is being developed by Cyclacel Pharmaceuticals, a University of Dundee spin-out that has received two previous rounds of Biomedical Catalyst funding.

Professor John Isaacs, Director of the Institute of Cellular Medicine at Newcastle University and lead investigator, said: “Repurposing of drugs is a potentially powerful way of bridging the gap between early stage research and development of a new treatment. Compared with traditional drug discovery approaches, this is a considerably cheaper and quicker route to the clinic because it 'leap-frogs' the early stages of drug development.

“If our trial proves successful it could dramatically improve the treatment outcomes for RA patients. It could also lead to further repositioning of similar drugs to treat other diseases such as cirrhosis and lung fibrosis, which will deliver additional benefits for the health service and the UK life sciences industry.”

Rheumatoid arthritis is a condition in which the joints become inflamed and painful. It affects about one in every 100 UK adults and is thought to be caused by the patient's immune system mistakenly attacking their joints. The resulting inflammation is not only painful but reduces joint movement and eventually causes joint damage and deformity.

Most drugs currently used to treat RA work by reducing the inflammation in the joint, or by neutralising cells of the immune system and their products. Over the past 20 years, improved treatment strategies and better drugs mean that the outcome for patients with rheumatoid arthritis has got better.

However, many patients still don't recover and about one in ten do not respond at all to conventional treatments. Scientists think that another type of cell – called fibroblasts – may be responsible for the arthritis symptoms in these patients; as well as limiting improvement in patients whose symptoms do respond to conventional treatments. In RA these cells divide uncontrollably and produce chemicals that eat into cartilage and bone and cause inflammation.

Using seliciclib to target fibroblasts

The Newcastle team, with collaborators at the Universities of Birmingham and Glasgow, will test a drug called seliciclib that they believe will reduce or stop abnormal fibroblast activity. Seliciclib works by blocking enzymes that are central to the control of the cell cycle, which stops fibroblast cells dividing. Seliciclib has been evaluated to date in approximately 380 cancer patients and is currently being tested in combination with another Cyclacel drug in cancer patients with solid tumours.

Researchers hope to show that the treatment is safe and potentially effective in RA. Initially they will treat patients who have had RA for at least a year and who are already taking treatment but not responding well enough. If this research is successful then they will test the treatment in RA patients taking different treatments, at different stages of their illness. The work will take place in Arthritis Research UK Experimental Arthritis Treatment Centres, which have been established in Newcastle, Birmingham and Glasgow.

Universities and Science Minister David Willetts said: “By investing in new technologies now we are maintaining the UK’s position as a world leader for innovation. The biomedical industry is a fast moving, high growth sector and the Catalyst has proven to be extremely successful in supporting new business ideas. This investment further drives forward our life sciences strategy.

“The new National Biologics Manufacturing Centre will significantly increase the UK’s manufacturing capability in biologics, keeping us ahead in the global race and strengthening the UK’s position as the location of choice for life sciences companies.”

Chief Executive of the Technology Strategy Board, Iain Gray said: “The Biomedical Catalyst programme has already proved a significant success, providing the support companies need to develop their innovations and solve healthcare challenges.
“The projects funded through this latest round of the programme demonstrate both the innovative nature of the UK’s health R&D sector and the success of the programme in identifying projects with strong commercial potential.”

published on: 31 July 2013