Can Translational Rheumatology Reinvent RA?

May 27, 2015

(CCR 2015) A new rheumatoid arthritis (RA) research center in the UK intends to revolutionize the understanding and treatment of the rheumatoid arthritis by 2020 by using systems biology to move beyond the one-molecule paradigm.

A new rheumatoid arthritis (RA) research center in the UK intends to revolutionize the understanding and treatment of the disease by 2020, “reinventing” the disease by “extending the paradigm of inflammatory biology to soft-tissue rheumatism,” Iain B. McInnes PhD told an audience at the Congress of Clinical Rheumatology 2015 in Destin, FL.

“We have spent a lot of money targeting therapeutic targets that were never there,” said McInnes. “Innovative approaches to academic-industry partnerships are now being tested to enhance target selection and validation.”

Researchers at the new Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence in Glasgow are collecting data from around the world for “translational rheumatology,” he said, intending to analyze it all systematically and gain a better understanding of why RA develops and persists.

For instance, “epigenetic factors, particularly microRNAs, regulate [RA] progression,” explained McInnes, who is director of the Institute of Infection, Immunity and Inflammation at the University of Glasgow. “Novel biologic mechanisms include microRNAs that cross-regulate discrete biologic pathways.”

The center, a partnership between the University of Birmingham, University of Glasgow, and the University of Newcastle, exists to “empower clinical rheumatologist to navigate data,” McInnes added, in a collaborative environment between biologists, specialists in bioinformatics, and clinical experts.  

McInnes’ recurring theme was a need for a revolution towards a systems approach. In vivo model systems can ask questions about how molecules and cells talk to each other, he observes, but not about tendinopathy itself.

Systems medicine could improve methods for stratifying patient subgroups in heterogeneous diseases, leading to improved diagnostics and therapeutic regimens.

In rheumatology, with the hundreds of known cytokines acting via many nodes of the inflammatory cascade, looking “molecule by molecule” is not useful, he said. “We need to understand the behavior of groups of molecules.”

“Current targets of development come from an antiquated system. We choose a molecule and go through a ponderous, quite often unsuccessful discovery paradigm. If we continue in this way, we will not get truly transformational alterations in the way we treat patients with rheumatic diseases,” he predicted.

But the next generation of rheumatology “will fail less often, and if we fail we will have an understanding why we failed so that we do better next time,” he went on. “That surely is the secret for future success.”