NIH Launches Major Coordinated Effort to Understand Lupus and RA

September 25, 2014

Backed by 6 drug firms and 4 foundations, the National Institutes of Health has created a large network of top researchers charged wtih collaborating to comprehend lupus and rheumatoid arthritis at the cellular and molecular level.

Weary of trying to pull together all the information about disease pathways into a sensible description of autoimmune dysfunction? So are the researchers themselves, and they've launched a massive coordinated effort to make sense of it all. They'll start with a focus on rheumatoid arthritis (RA) and lupus.

The National Institutes of Health yesterday announced awards of $6 million in grants, joining 11 top-rank research groups across the United States in a huge collaborative effort to share data and tissue samples. The goal is to define the biology behind the two diseases (and also, presumably, others) and identify new drug targets as a result.

The initiative answers longstanding and repeated pleas from researchers in immunology and rheumatology for data sharing and for integration of tissue sampling with disease registries.

Coordinated by the National Institutes of Health, the new AMP RA/Lupus (Accelerating Medicines Partnership in Rheumatoid Arthritis and Lupus) Network is a joint venture supported by six pharmaceutical firms (AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Sanofi, Takeda) and four foundations (the Arthritis Foundation, the Lupus Foundation of America, the Lupus Research Institute/Alliance for Lupus Research, and the Rheumatology Research Foundation).  The partners have agreed to make all AMP data and analyses broadly available to the entire biomedical research community.

NIH director Francis Collins MD PhD calls it an “unprecedented approach to identify pathways that are critical to disease progression in rheumatoid arthritis and lupus.”

The collection of genetic data will focus on patients with lupus or RA, as well as unaffected individuals. Tissue samples will primarily include synovium from RA patients, kidney tissue from lupus patients, and blood.

Two types of research sites, clinical and technology, are being funded, as well as some that combine the two:

Clinical:

Jennifer H. Anolik MD PhD at University of Rochester will obtain synovial tissue from RA patients and analyze microscopic structure, function, and interactions of affected tissues and cells (including subchondral bone and marrow).

Researchers at New York’s Hospital for Special Surgery (Vivian Bykerk MD, Lionel B. Ivashkiv MD, and Alessandra B. Pernis MD) and Robert B. Darnell MD PhD  of the New York Genome Center will cooperate with researchers at the University of Toronto to obtain paired samples of peripheral blood and synovial tissues from RA and control patients, as well as contributing to efforts to find biomarkers of flares and drug response in RA.

Peter Gregersen MD at the Feinstein Institute for Medical Research, collaborating with others from Europe, will obtain and analyze synovial tissue from RA patients using cutting-edge technologies.

Larry W. Moreland MD at the University of Pittsburgh will amass data with accompanying tissue samples from clinical registries, including a large cohort of RA patients under the care of a single network of rheumatologists in Pittsburgh.

Michelle Petri MD MPH at Johns Hopkins University will provide specimens and data from the Hopkins Lupus Cohort, as well as comparison samples from people with osteoarthritis, gout, and other autoimmune diseases.

Technology research:

Michael B. Brenner MD and Soumya Raychaudhuri MD PhD at Brigham & Women’s Hospital will conduct bioinformatics and computational analyses and develop and apply systems biology approaches to improve understanding of autoimmune diseases.

William H. Robinson MD PhD and Paul J. Utz MD at Stanford University will study B and T cells in blood and tissues to identify genes, proteins and pathways that are abnormal in lupus and RA.

Combined clinical and technology:

Three New York City centers--Jill P. Buyon MD at New York University School of Medicine, Chaim Putterman MD at Albert Einstein College of Medicine, and Thomas Tuschi PhD at Rockefeller University will use the METRO Lupus Consortium cohort to study effects of race and ethnicity on specific biological pathways and drug targets in lupus. They will also provide normal skin samples from lupus nephritis patients to try to find noninvasive ways to identify early kidney damage.

Betty A. Diamond MD of the Feinstein Institue and David Wofsy MD at University of California San Francisco will work with the Lupus Nephritis Trials Network to collect and characterize tissue samples using cutting-edge technologies.

V. Michael Holers MD at the University of Colorado will study evolution of cellular and molecular changes accompanying RA progression, as well as developing ultrasound-guided synovial biopsy techniques and training other researchers to use them.

Drs. Utz of Stanford and Holers of the University of Colorado will share leadership of the effort, which is planned in three phases:

Research Phase 0:  Testing different means of obtaining and prepping tissue samples as well as developing standard methods of analysis.

Research Phase I:  Analysis of standardized analytics from Phase 0, with at least one study each in RA and lupus to be completed by the end of the second year. This phase will also include assessing samples from people who do not have RA or lupus, looking to distinguish diseased tissue from normal tissue.

Research Phase II:  Testing in larger patient populations, with patients stratified according to many criteria such as disease phase, pre-and-post treatment status, and treatment response.

“The AMP RA/Lupus Network has developed an innovative, collaborative project that has tremendous potential to improve patient care," said Mary Wheatley, Executive Director of the Rheumatology Research Foundation, the research funding arm of the American College of Rheumatology, in a prepared statement. "It is our hope that this collaboration will lead to improved outcomes in lupus and RA, and that the lessons learned and information gathered can be applied to other disease areas.”