New drug target to fight RA
role in the fight against autoimmune diseases with the possibility
of developing this compound into a practicable treatment for
rheumatoid arthritis (RA), which currently afflicts one per cent of
the world's population.
The potential of this candidate is made all the more urgent as increasing numbers of patients are becoming unresponsive to Disease-Modifying-Anti-Arthritis Drugs (DMARDS), the first line therapies for RA. Findings from this research may lead to highly specific medicines aimed at the root causes of autoimmune diseases and rejection reactions following organ transplantation.
Biological agents such as the tumour necrosis factor (TNF alpha) blockers Enbrel, Remicade and Humira are now established treatments for patients. However, up to 40 per cent of patients fail to respond to these agents or respond until neutralizing antibodies develop as a consequence of repeated dosing.
In this latest study researchers found the class II associated invariant chain peptide (CLIP) lowered the production of immune system cells that produce pro-inflammatory immune responses, including autoimmunity.
The potential pharmacological importance of this discovery comes from the fact that modulating levels of CLIP may be used to modulate the immune response itself.
Harald Kropshofer, Roche's head of non-clinical immunology said: "RA belongs to the group of autoimmune diseases that depend on the expansion of a subset of blood cells, the helper T lymphocytes (TH1)."
"Particular TH1 cells contribute to autoimmunity by recognizing proteins of our own body, triggering adverse immune system reactions against the body's own tissues. TH1 cells secrete substances that trigger, mediate and maintain autoimmune diseases."
"A peptide that helps to lower the generation rate or abundance of these TH1 cells could be an extremely helpful approach in RA therapy."
The team showed that the dendritic cells of the immune system turn on CLIP on the cell surface, which reduces the number of helper T cells changing to the TH1 type.
CLIP appeared to function as a novel type of peptide regulator. More significantly, they found that synthetic CLIP had the same function as naturally occurring CLIP.
This opens up the possibility of using synthetic CLIP as therapeutic agents. CLIP mediates its activity by binding to molecules of the major histocompatibility complex (MHC) class II, which are being viewed as risk factors for RA and other autoimmune diseases.
RA is one of the most common forms of autoimmune disease that leads to painful inflammation and ultimately destruction of bone joints. It affects 2.1 million Americans, of which 1.5 million are women compared to 600,000 men. Onset is usually in middle age, appears more frequently in older people, but also affects children and young adults.
Musculoskeletal conditions such as rheumatoid arthritis cost the U.S. economy nearly $86.2 billion (€70.9 billion) per year in medical care and indirect expenses such as lost wages and production.
