Scripps research combination therapy obliterates new vessel growth in tumors and retinopathy

Using a new and dramatically effective treatment approach, scientists at the Scripps Research Institute have for the first time achieved complete inhibition of new blood vessel growth in animal models of a highly vascular brain tumor and of neovascular eye diseases with little or no effect on normal tissue vasculature.

The paper is being published online this week in the Proceedings of the National Academy of Sciences.

“While a number of new drugs that inhibit new blood vessel growth are now available in the clinics, no one so far has been cured with available anti-angiogenic agents,” said Professor Martin Friedlander, a Scripps Research scientist and retina specialist at Scripps Clinic who led the study. “Our study shows that combining anti-angiogenic agents that target multiple angiogenic pathways can significantly increase the effectiveness of such a therapeutic approach. Such combination angiostatic therapy provides a whole new range of treatment options for patients with neovascular diseases, where complete inhibition of new blood vessel growth is the desired result.”

While new blood vessel growth from preexisting capillaries (“angiogenesis”) is fundamental to survival, the abnormal formation of new blood vessels (“neovascularization”) contributes to the pathogenesis of tumor growth and metastasis as well as the vast majority of diseases that lead to catastrophic loss of vision. A number of angiostatic molecules have been used to impair blood vessel formation as clinical adjuncts to conventional radio- and chemotherapy. Others have proven to be modestly effective in treating neovascular eye diseases.

The new study combined the actions of three classes of angiostatic compounds, each targeting different angiogenic pathways, and showed striking results in the treatment of an animal model of glioblastoma, a highly malignant brain cancer, and ischemic retinopathy, excessive blood vessel growth in the eye that is a major cause of blindness worldwide.

“Our combination therapy reduced tumor mass and increased survival in the glioblastoma model,” Friedlander said. “In models of neovascular eye diseases, the therapy resulted in complete inhibition of pathological neovascularization in more than 60 percent of the eyes; over 90 percent had greater than 75 percent inhibition of new vessel growth with no adverse affects on normal tissue vasculature. In contrast, individual therapies with comparable doses of individual drugs were minimally effective, if at all.”

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Scripps research combination therapy obliterates new vessel growth in tumors and retinopathy
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