In a new approach to treating rheumatoid arthritis (RA), researchers found that drugs delivered into the central nervous system worked better in the treatment of rheumatoid arthritis, at least in arthritic rats. In the research carried out on arthritic rats, the researchers delivered the drug directly into the spinal cord to block the p38 protein, a protein critical to the development of RA. The findings of the research done by Gary Firestein and colleagues from University of California, San Diego have been reported in the international open-access medical journal PLoS Medicine.
Rheumatoid arthritis is a disease marked by chronic inflammation, leading to joint pain and destruction. Pain and inflammation in the joints are constantly monitored by the central nervous system (CNS, i.e. the brain and spinal cord). Scientists have long suspected that the CNS can regulate inflammation and immune responses in the body's "periphery", but little is known about how this works. Firestein and colleagues focused on a protein called p38, which is involved in a number of cellular processes critical to the development of RA. Several substances that block the action of p38 are effective in animal models of arthritis and are currently being tested in clinical trials in patients with RA.
These findings suggest that spinal cord administration might reduce the side effects (and possibly the costs) of p38 inhibitors without compromising the benefits to patients. And if future studies confirm that the action of these drugs on the CNS is essential to achieve a response even when administered as a systemic treatment, designing drugs that get into the CNS easier might improve the effectiveness and/or make it possible to use lower doses systemically.
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