Five Within Our Reach science investigators provided overviews and updates of their RA research projects to the newly formed Within Our Reach advisory board at its inaugural meeting, held November 8, 2007.
The meeting gave advisory board members an opportunity to interact with these award recipients, seeing just how their donor dollars have been used and appreciating the impact of financial support from the Within Our Reach campaign. Here are some highlights from the recipients’ presentations.
- Joan M. Bathon, MD, professor of medicine at Johns Hopkins Arthritis Center in Baltimore, discussed her research on rheumatoid arthritis and body composition:
RA is highly inflammatory chronic disease that significantly diminishes physical function and causes premature mortality, primarily through accelerated cardiovascular disease. It has been shown that body composition is adversely affected in RA, as reflected by a reduction in lean (muscle) mass and in an increase in fat mass. Fat itself is a potent source of proinflammatory cytokines and adipokines, and increased fat mass is associated with insulin resistance and cardiovascular events in the general population.
Dr. Bathon’s study will lay the groundwork for clinical recommendations and interventions to identify and reverse adverse body composition, and will set the stage for clinical trials to investigate the effect of modifying body composition on morbidity and mortality in RA.
- Gary S. Firestein, MD, professor of medicine; chief of rheumatology, allergy, and immunology; and director of the Clinical Investigation Institute at the University of California, San Diego, School of Medicine, provided updates on his research on neural regulation of synovial inflammation:
Many of the therapies currently available for RA focus on the role of the immune system and its regulation of synovial inflammation and joint destruction. Dr. Firestein’s lab has discovered a novel pathway that allows the central nervous system to communicate with the immune system and decrease joint inflammation and destruction. His recent studies suggest that blocking a specific protein kinase in the central nervous system may enable regulation of the vagus nerve and release of certain acetylcholine receptors, which in turn can limit tumor necrosis factor (TNF) production and inflammation. If this hypothesis is correct, a new class of agents could be developed to regulate functions in the spinal cord and brain to decrease joint inflammation and joint destruction.
- Antony Rosen, MD, Mary Betty Stevens professor of medicine, professor of cell biology and pathology, and director of the division of rheumatology at Johns Hopkins University School of Medicine in Baltimore, discussed his research on anti-PADI4 immune responses in RA:
Recent discoveries have provided important new therapies for RA by identifying novel pathways that drive disease and generate tissue damage. This study will focus on an important and previously unrecognized immune response in RA. PADI4 is one of the major proteins that create other common autoantigens in RA. Dr. Rosen hopes to define the use of new blood tests to monitor disease activity and outcome and investigate why the disease-associated form of PADI4 is chosen for immune attack. This information may help to define and monitor a critical event occurring in early RA that causes the disease to amplify.
- Cornelia M. Weyand, MD, PhD, David Lowance professor of medicine and director of the Lowance Center for Human Immunology at Emory University in Atlanta, discussed her research on defects of hematopoietic stem cell function in RA:
Although our ability to treat RA with potent antiinflammatory medications has increased enormously, the cause of this disabling syndrome remains unresolved. Dr. Weyand’s study builds on preliminary data, which suggest that hematopoetic precursors cells are defective in frequency and function in most RA patients. She believes this identifies bone marrow as the primary site of RA pathology. Her research will examine precursor cell function in RA and focus on how these cells engraft and build the different types of blood and immune cells.
Dr. Weyand’s team will investigate how treatment with methotrexate or TNF blockers affects bone marrow precursor cells to determine where the defects in these cells exist. The ultimate goal is to develop a totally novel approach to RA, aiming at regeneration of bone marrow precursor cells to improve function and tissue repair.
- David M. Lee, MD, PhD, assistant professor of medicine at Brigham and Women’s Hospital in Boston, discussed his research on immunoglobulin G (IgG) glycosylation and RA:
This project will investigate the usefulness of a new laboratory test measuring a natural modification of antibodies (glycosylation) in patients with rheumatoid arthritis. By employing a new methodology, Dr. Lee hopes to determine the utility of IgG glycosylation (a natural modification of antibodies) as a biomarker for diagnosis, prognosis, and prediction of response to therapy in RA. If measurement of IgG glycosylation proves a useful biomarker in patients with RA, the newly developed methodology is readily transferable to clinical practice. It could aid in early diagnosis of the disease, or help predict disease severity and which patients will respond to specific medications.
The Within Our Reach advisory board was created to provide a forum for interaction between lay and other campaign donors, leadership, and science investigators. This was of great importance to Dr. Lee, as he saw this as an opportunity to thank the advisory board for their support of the Within Our Reach campaign, which—according to Dr. Lee—has enabled work on a novel and exciting disease pathway in RA. “Because of the Within Our Reach campaign, we have been able to put together the resources and personnel to move forward,” says Dr. Lee. “It is quite likely this funding mechanism will enable RA-focused research projects that previously languished for lack of appropriate funding.”
Within Our Reach is a multi-year, $30-million fundraising campaign seeking to advance the future of rheumatologic research by accelerating RA research not normally funded by the National Institutes of Health (NIH) or other peer-reviewed funding sources.
Launched by the ACR Research and Education Foundation (REF) in March 2006, Within Our Reach has the capacity to improve RA patients’ quality of life, alleviate long-term effects of RA, and, ultimately, ensure that future generations can enjoy life without RA.
For more information on the Within Our Reach campaign, visit www.WithinOurReach.info.
Within Our Reach Leadership Supporters
The REF gratefully acknowledges the following companies and individuals who have demonstrated leadership support for the Within Our Reach campaign. This information was current as of January 11:
Pinnacle ($5 million+):
- Abbot Immunology
- ACR
- Bristol-Myers Squibb
Partner ($1 million+):
- Genentech, Inc.
Milestone ($250,000–$499,999)
- J. Peter Cahill (in memory of Carol K. Cahill)
- Shirley and Hunter Enis
- Betsy and John McLinden
Visionary ($100,000–$249,000):
- Anonymous
- The Hersh Foundation
- Myles McDonough
- Sandra and Alan Williams