At the 2008 Congress of European Pharmacological Societies (EPHAR), held July 13-17, 2008 in Manchester, England, Professor Marc Feldmann of the Imperial College London predicted that drugs he helped develop to treat rheumatoid arthritis may prove to be effective for many more medical conditions, including atherosclerosis.
The drugs, which block a cytokine known as tumor necrosis factor-alpha (TNF-alpha), include infliximab, etanercept and adalimumab, which have shown a dramatic protective effect in patients afflicted with rheumatoid arthritis, an autoimmune disease. These agents have also shown to be of benefit for other autoimmune and inflammatory conditions, including Crohn's disease, psoriasis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis. Additionally, they have shown promise in the treatment of acute alcoholic hepatitis, a potentially fatal condition.
Cytokines such as TNF-alpha are molecules released by immune cells to alert the immune system that the body is under attack and to initiate a response against the infection. "In autoimmune diseases, such as arthritis, we discovered that cytokines are over-produced causing the immune system to fight itself, resulting in inflammation and tissue destruction," Dr Feldmann explained. "We further found that by blocking just one cytokine – tumor necrosis factor alpha – we were able to block all the cytokines involved in the inflammation, with remarkable clinical results."
Dr Feldmann believes that similar drugs may have the potential to treat many other conditions, and is currently researching their effect on atherosclerosis. Atherosclerosis, he explained, “is caused by a chronic inflammatory response in the walls of the arteries, in large part, caused by an excessive immune response to cholesterol."
In research recently reported in BMC Neurology, Edward L. Tobinick, MD, of the Institute for Neurological Research in Los Angeles, and Hyman Gross revealed new data from of a trial of etanercept in Alzheimer’s disease patients with verbal impairment. Weekly perispinal injection of the drug for a six month period resulted in significant improvement in several verbal test scores. In two case histories detailed in the current report, benefits occurred within minutes of injection.
Recent evidence suggests that TNF-alpha regulates synaptic function in the brain. “The scientific rationale for the further investigation of anti-TNF-alpha treatment of Alzheimer's disease is compelling,” Dr Tobinick stated. “In addition, family members, independent neurologists, and other independent observers have confirmed the clinical, cognitive, and behavioral improvement noted".
Dr Feldman’s work has resulted in a new branch of medicine termed anti-cytokine therapy. He notes the possibility that “cytokines play a critical role in all diseases involving multiple biological processes, thus providing therapeutic targets for all unmet medical needs.”
Aging results in an increase of inflammatory cytokines (destructive cell-signaling chemicals) that contribute to the progression of many degenerative diseases (Van der Meide et al. 1996; Licinio et al. 1999). Rheumatoid arthritis is a classic autoimmune disorder in which excess levels of cytokines such as tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), interleukin 1b [IL-1(b)], and/or interleukin-8 (IL-8) are known to cause or contribute to the inflammatory syndrome (Deon et al. 2001).
Chronic inflammation is also involved in diseases as diverse as atherosclerosis, cancer, heart valve dysfunction, obesity, diabetes, congestive heart failure, digestive system diseases, and Alzheimer's disease (Brouqui et al. 1994; Devaux et al. 1997; De Keyser et al. 1998). In aged people with multiple degenerative diseases, the inflammatory marker, C-reactive protein, is often sharply elevated, indicating the presence of an underlying inflammatory disorder (Invitti 2002; Lee et al. 2002; Santoro et al. 2002; Sitzer et al. 2002). When a cytokine blood profile is conducted on people in a weakened condition, an excess level of one or more of the inflammatory cytokines, e.g., TNF-a, IL-6, IL-1(b), or IL-8, is usually found (Santoro et al. 2002).
Prescription drugs like Enbrel directly bind to TNF-a and block its interaction with TNF cell surface receptors. Enbrel has demonstrated significant clinical improvement in rheumatoid arthritis patients, as have high-dose fish oil supplements (Kremer 2000).
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