A large-scale genomic study published in the July 29 issue of the New England Journal of Medicine reports that genetic variations in two genes — the IL-2 and IL-7 receptors — may be linked to multiple sclerosis. Additionally, the applicability of these receptors in various disease settings may eventually make them attractive for targeted therapeutic and diagnostic development for pharmaceutical and diagnostics companies, one of the study authors said.
The study, conducted by an international consortium of scientists, “is the first comprehensive study investigating the genetic basis of MS,” according to a statement from the Montreal Heart Institute at Université de Montréal, one of the organizations involved in the research.
Although the association of IL-2 and IL-7 with MS risk is a new finding in this study, IL-2 had been previously associated with the risk of type 1 diabetes and autoimmune thyroid disease. Additionally, IL-7’s impact on the immune system has been explored in two papers published in Nature Genetics.
“It’s always a difficult challenge to give a prediction whether a diagnostic or therapeutic,” will result from a study, John Rioux, associate professor of medicine at the Montreal Heart Institute and a study author, told Pharmacogenomics Reporter this week. However, “some of the genetic risk factors being shared in multiple different diseases might indicate that targeted therapies for one disease might actually work for other diseases as well,” he said.
“There is a limited pot of money for any pharmaceutical company, so hopefully seeing [that] there are these common genetic risk factors will … encourage them to put some efforts into some of those particular pathways,” for therapeutic or diagnostic development, Rioux added.
In the coming era of personalized medicines, pharma’s answer to the battle-weary blockbuster is the niche-buster [see PGx Reporter 03-28-2007]. Instead of investing heavily in drugs that treat diseases in broad populations, large pharmaceutical companies such as Bristol-Myers Squibb, Lilly, and Novartis are focusing on identifying biomarkers that target subpopulations in multiple disease markets.
The authors involved in the study hail from Brigham and Women's Hospital, Harvard Medical School, Harvard Partners Center for Genetics and Genomics, Harvard Center for Neurodegeneration and Repair, the Broad Institute of Harvard University and Massachusetts Institute of Technology, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Massachusetts General Hospital, Duke University Medical Center, Université de Montréal, Vanderbilt University Medical Center, the University of California at Berkeley, and the University of California at San Francisco.
Analyzing genomic information from 12,360 people, the study confirmed that genes linked to the immune system are altered in MS patients. Additionally, researchers conducted genome-wide association studies on 931 sets of DNA samples from MS patients and their parents, and looked at 500,000 SNPs on the Affy 500K platform to try to identify the most common genetic variations in MS patients compared to people without the disease.
To validate the findings, researchers also studied other sets of families, individual cases of MS, and a control group, bringing the total number of study subjects to more than 12,000 people.
“There is a limited pot of money for any pharmaceutical company, so hopefully seeing [that] there are these common genetic risk factors will … encourage them to put some efforts into some of those particular pathways.”
Until this research, “the only genetic link for MS previously identified using other techniques is in the major histocompatibility complex, a large cluster of genes responsible for many immune functions, including preventing the body's immune cells from attacking its own tissues,” the Montreal Heart Institute said in a statement. “This analysis confirmed that link but went further to find other variants in genetic regions that are more common in people with MS.”
Rioux wouldn’t say exactly how much the study cost, but said that the study was “expensive” given that 931 patients had to be screened. The study was funded with grants from the National Multiple Sclerosis Society, the National Institutes of Health, and the Penates Foundation.
The broad applicability of IL-2 and IL-7 will likely spur researchers to look at connections between autoimmune diseases. For this, future studies would need to be expanded to include more research organizations, more patients, and more samples.
“Based on our own studies in Crohn’s disease and other studies from my colleagues in different disease areas, it’s clear that the larger the sample size, the better the power to identify genes,” Rioux said. “We’ll have to increase the sample size of this study. That will most likely be done by broadening the collaboration with other groups.”
In the NEJM study, researchers genotyped 500,000 genes, but they found only 32 that were highly suggestive of being associated with MS and validated those. However, “if we [had] a larger number of individuals [and identified] a larger number of SNPs that we tried to replicate, we would probably identify more genes,” Rioux noted. “We could definitely go deeper into the current results. That’s something we’re trying to do by increasing the collaboration.”
According to Rioux, the study would not have been possible without extensive collaboration with research institutions across the globe. All the data will be made publicly available so that others researchers can access the information, he said.