The American Autoimmune Related Disease Association lists over 50 different autoimmune diseases. Some of these are common such as rheumatoid arthritis which affects about 1% of all populations, women two to three times more often than men. This translates to a total of 5 million sufferers in the major pharmaceutical markets. The market for agents used to treat rheumatoid arthritis totaled $1.6 billion in 2000. According to some analysts, new therapeutic approaches will drive the market for autoimmune disorders such as rheumatoid arthritis to grow at a rate of over 15%, to a value of over $21 billion by 2006. At present, treatments of this disease are based on symptomatic therapies such as NSAIDs however new therapeutic directions are emerging. One example is the use of bisphosphonates, which reduce bone erosion and were originally indicated for osteoporosis. A second field that has been attracting considerable attention is angiogenesis since this process is overactive in rheumatoid arthritis. Recent data emerging from researchers at Novartis is therefore of considerable interest. This group has demonstrated that zoledronic acid, a new generation bisphosphonate with a heterocyclic imidazole substituent, is also a potent inhibitor of angiogenesis. In vitro, zoledronic acid inhibits proliferation of human endothelial cells, and modulates endothelial cell adhesion and migration. In cultured aortic rings and in the chicken egg chorioallantoic membrane assay, zoledronic acid reduces vessel sprouting. When administered systemically to mice, zoledronic acid potently inhibits the angiogenesis induced by subcutaneous implants impregnated with bFGF. These findings indicate that zoledronic acid may be of use in the treatment of arthritis as a result of its ability to reduce both bone erosion and angiogenesis. Perhaps more importantly, angiogenesis is a major contributor to the progression of cancer. Patients with advanced tumors frequently develop painful bony metastases. A number of bisphosphonates are already in use to reduce metastatic pain, however this data suggests that earlier treatment initiation may slow disease progression adding further benefit to this therapeutic class. This concept is further supported by earlier data describing the pro-apoptotic as well as the anti-proliferative, -adhesive, and -invasive activity of bisphosphonate treatment of breast cancer cells.

Entry date October, 2002

Adapted from Wood et al, J Pharmacol Exp Ther 2002 Sep;302(3):1055-61-

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