Cambridge scientists have made a major breakthrough in rheumatoid arthritis. They have genetically engineered a drug-inducible form of Foxp3 gene, which when activated can prevent the autoimmune reaction characterised by the disease.
Rheumatoid arthritis is a painful, inflammatory type of arthritis that occurs when the body's immune system attacks itself.
And the new strategy developed by scientists at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, may open the door for therapy development for rheumatoid arthritis.
Generally, immune cells develop to recognise foreign material - antigens; including bacteria - so that they can activate a response against them.
Immune cells that would respond to 'self' and therefore attack the body's own cells are usually destroyed during development. If any persist, they are held in check by special regulatory cells that provide a sort of autoimmune checkpoint.
And Foxp3 plays a major role in these regulatory cells. People who lack or have mutated versions of the Foxp3 gene, lack or have dysfunctional immune regulation, which causes dramatic autoimmune disease.
By genetically engineering a drug-inducible form of Foxp3, the scientists can now 'switch' developing immune cells into regulatory cells that are then capable of suppressing the immune response.
"We have generated a modified form of Foxp3 which can be introduced into immune cells using genetic engineering techniques and then activated by a simple injection. When administered to and activated in animal models of arthritis, the modified cells inhibit or even reverse the disease process," said Dr. Alexander Betz, Group Leader at the MRC laboratory.
Now, more work is aimed at explainong the detailed molecular mechanisms involved in Foxp3 function, and transferring the experimental approach to human cells.
"First, we will develop a human Foxp3 factor and then assess its function in human arthritis models. To be viable as a therapeutic option, the regulatory cells must fulfill certain criteria; they must be tissue matched to the patient for compatibility; they must only block the targeted disease and not the whole body immune response; and they have to home correctly to their target tissue. Establishing these criteria will be the key focus of our research," said Dr Betz.
He added: "If Foxp3 functions as a key developmental switch in human immune cells, there is potential for a new avenue of therapy development that could transform arthritis treatment is substantial," he added.
The study is published in the latest issue of PLoS Biology.