Novel treatment for angiogenesis-related diseases.
Angiogenesis, the growth of new blood vessels from pre-existing vasculature, has an essential role in development, reproduction and repair. Pathological angiogenesis is a common theme in a broad range of diseases such as cancer, autoimmune diseases, age-related macular degeneration and atherosclerosis. The global market for angiogenesis stimulators and inhibitors is forecast to reach ~US $50 billion by the year 2015. Most of the currently marketed angiogenesis regulators, such as Avastin, typically display modest efficacy and therefore further highlight the great need for the development of novel therapeutics. The current technology presents a novel method to treat angiogenesis-related disorders by modulating apolipoprotein B (ApoB).
· ApoB is a potential therapeutic target for the treatment of cancer and other non-neoplastic diseases.
· ApoB levels may serve as a biomarker for cancer metastasis.
· The anti-angiogenic effect of LDL administration was demonstrated in vivo, in zebrafish models, as well as in vitro,in relevant human cells lines.
· Regulation of ApoB levels may be applied to treat a broad range of angiogenesis-dependent diseases.
· Detection of ApoB levels can be readily achieved by analysis of body fluids such as blood and plasma.
Using a high-throughput genetic screen for vascular defects in zebrafish, researchers at the Weizmann Institute of Science have identified a genetic mutation that leads to excessive angiogenesis. The mutated gene is responsible for the assembly of ApoB-containing lipoproteins such as LDL, otherwise known as the 'bad' cholesterol. The group has found that low levels of LDL promote the formation of new blood vessels by directly interacting with the VEGF pathway. The outlined technology offers methods to modulate the levels of ApoB in order to stimulate, or inhibit angiogenesis, dependent on the therapeutic strategy. For example, inhibition of angiogenesis by increasing ApoB levels may repress tumor growth and attenuate its metastatic potential. In another application of this technology, increased circulating levels of ApoB can serve as a biomarker for the overproduction of blood vessels, thus enabling early diagnosis of pathogenic states in angiogenesis-dependent diseases.