Additionally, translational research efforts are most likely to succeed using a team approach, Dr. McInnes said. "It is essential to recognize the different disciplines necessary to properly address the complex issues in human disease," he stressed. "The team requires people coming together and being prepared to work together and possibly change their own way of thinking a little bit."
Efforts to foster such teams – particularly across public, private, and corporate sectors – can be hindered by administrative roadblocks, including concerns about obtaining consent from patients, intellectual property issues, and who stands to gain from knowledge obtained from any given study," Dr. Cronstein said. In addition, the "demonization" of the pharmaceutical industry in recent years "makes it difficult to collaborate with pharma without being penalized or at least having to run a major gauntlet of paperwork and review," he said. "Clearly, pharma will try to obtain a benefit for itself, but we can collaborate successfully to develop new drugs and new understanding of the diseases of the patients we care for."
At the end of the day, rheumatology is poised to gain much from such efforts. "The field of rheumatology stands to gain new understanding of the diseases that afflict our patients, new therapies for these diseases, and novel targets for development of drugs that can benefit our patients," said Dr. Cronstein. "The advantages of collaboration are overwhelming and the danger of fragmentation of efforts is critical."
The Translational Journey of JAKs
"Some of the most exciting translational research in rheumatology right now is the use of intracellular signal proteins as targets of small-molecule drugs," said Dr. McInnes. "There’s irony in this, because rheumatologists use small-molecule inhibitors all the time, including methotrexate and sulfasalazine. The difference is we’re now using new molecular entities that have been designed specifically to seek out some of the signal pathways that very elegant biology over the last 10-20 years has shown to have a role in inflammation."
The work by Dr. John O’Shea on cytokine signal transduction and the roles of janus kinases (JAKs) and signal transducer and activator of transcription (STAT) factors in immune cell development and differentiation are an excellent example, Dr. McInnes said. The research by Dr. O’Shea, scientific director of the intramural research program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health in Bethesda, Md., led to an NIH patent related to JAKs as a new class of immunosuppressive drug. Through a cooperative research agreement with Pfizer, a JAK3 compound (tofacitinib) is currently in phase III trials.
"These drugs are still not licensed, but the [translational] success story is that the proof of concept that JAKs are involved in the pathogenesis has been achieved," Dr. McInnes said. "When you block [the molecules], patients get better. That doesn’t mean you’ve got a drug, but it does tell you the biology pans out pretty well."
The research developments in this scenario were very much driven around the science of the JAKs initially, "then the investigators looked at people whose immune systems didn’t work very well to see if JAKs were deficient in them, which they were," Dr. McInnes explained. "The next step was to flip back to the lab to consider whether that information could be therapeutically useful, and eventually it found its way back to rheumatology practice.
"Although we still don’t know all that much about how these pathways work in rheumatoid tissue," Dr. McInnes said, "the translation journey [of JAKs] thus far "is one to be admired."
Dr. McInnes and Dr. Cronstein reported no relevant conflicts of interest.