One gene, three diseases
KAROLINSKA
SEEKING RESEARCH SUPPORT
A Karolinska team confirms that a common gene contributes to multiple sclerosis, rheumatoid arthritis and – surprisingly – heart attack. The research could improve trials of new treatments for these diseases, including statins, now used to lower cholesterol, and lead to new diagnostic tools.
Dr. Fredrik Piehl and colleagues at Karolinska Institutet’s teaching hospital in Stockholm have found that patients with a particular allele of the MHC2TA gene have a 20% to 40% higher risk of development of multiple sclerosis, rheumatoid arthritis and other auto-immune diseases. That this is so for multiple sclerosis and rheumatoid arthritis simply confirms researchers’ expectations – but more surprising was their finding that the same gene also appeared to be linked with the most common form of heart attack, myocardial infarction. The gene is apparently common, in 20% to 25% of the population.
After reporting their latest findings in Nature Genetics and filing patent applications, they are now seeking corporate sponsors to push their work further.
It had long been suspected that a particular group of genes, controlling expression of a piece of the immune system called Major Histocompatibility Complex Class II, is involved in the development of multiple sclerosis, rheumatoid arthritis and other auto-immune diseases. In a 2003 paper in the Journal of Neuroscience, Dr. Piehl, with his former professor Tomas Olsson of Karolinska and others, identified a specific locus on the rat genome that appeared to regulate MHC expression. Since then, they have been studying human patient records in Sweden to spot the same gene, and look for a correlation with auto-immune diseases.
The discovery of a link between the MHC2TA gene and auto-immune diseases is good news to two Phase II clinical trials now underway in Scotland and the U.S. to test the effectiveness of a common class of cholesterol-lowering drugs, statins, in MS and arthritis. It has been known for some time that statins appear to affect this particular gene, and so Piehl’s research could provide an explanation of how. It also, he says, creates the possibility of targeting statins specifically to those patients with the suspect gene. “Since this gene is druggable with statins, one would like to see (in further research) whether those patients having the genotype have a better or worse response” to the drugs, says Dr. Piehl.
Other researchers in the field have taken note. “It’s potentially useful – it could work” in treating the diseases, says Prof. Rikard Holmdahl, of the University of Lund, Sweden. He notes much work remains to be done, including breeding rats that can serve as animal models to test the drugs. Among other unanswered questions: As the research focused on Swedish patients, will the same findings hold in a less homogeneous population?
So far, the research has been funded by a variety of public bodies and foundations in Sweden. “Our interest is in getting (corporate) funding for more research to exploit this finding,” says Dr. Piehl.
