Researchers identify potential new RA pathway
rheumatoid arthritis (RA) that could provide unique insights into
the disease process and eventually a new approach to developing RA
therapies.
RA affects approximately 0.5 to one per cent of the adult population worldwide and about twice as many women as men suffer from the disease. Currently, Enbrel (etanercept) and Remicade (infliximab) dominate the US and European RA markets, accounting for more than 80 per cent of value sales.
Studies conducted by Biogen and University of Geneva scientists have revealed that inhibiting the TWEAK molecule may interrupt the disease through a series of multiple mechanisms.
"Despite considerable progress, many rheumatoid arthritis patients do not adequately respond to current treatments, indicating that other pathways are involved in this complex disease," said Timothy Zheng, senior scientist, molecular discovery at Biogen.
"Our investigative research suggests the TWEAK pathway may also represent a new set of opportunities for treatment."
TWEAK belongs to a family of molecules called tumour necrosis factor (TNF) that plays an important role in normal immune system and inflammatory responses.
TNF-inhibiting therapies are currently used to treat a number of diseases including RA, a chronic, autoimmune disease that causes inflammation and swelling of the joints and the surrounding synovial tissue, resulting in progressive damage to the cartilage and bone.
TWEAK stimulates blood vessel growth (angiogenesis) and production of inflammatory proteins called cytokines and chemokines.
The published studies found that TWEAK promotes a number of events that are hallmarks of RA, including joint inflammation and synovial angiogenesis (blood vessel growth in joints).
Specifically, Biogen researchers found that TWEAK promotes joint inflammation by stimulating the production of several types of inflammatory proteins, triggers joint damage by stimulating the production of damaging metalloprotease enzymes and promoting bone breakdown, and contributes to joint tissue disease by directly promoting angiogenesis in synovial tissue.
The studies also suggest that TWEAK may impede normal bone repair mechanisms.
"Our research is part of a broader effort to identify the role of the TWEAK pathway in several autoimmune diseases," added Linda Burkly, the TWEAK program leader at Biogen.
Current treatments for RA are varied with local steroid injections, joint replacements used to treat the symptoms. Seldom did the therapies make the pain go away completely or for very long, nor did they affect the underlying joint damage.
However, much progress has been with drugs called biologic response modifiers or biologics. This group of drugs include, Enbrel, Humira, Kineret, Remicade, Rituxan and Orencia.
Enbrel, Humira, and Remicade inhibit a cytokine called tumor necrosis factor or TNF. Kineret blocks the cytokine interleukin-1 (or IL-1). Rituxan selectively targets immune cells known as CD20-positive B cells.
