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Bevacizumab: VEGF neutralization can damage brain vessels

New research at Schepens Eye Research Institute may help explain why the anticancer drug Avastin ( Bevacizumab ), which targets a growth factor responsible for creation of new blood vessels ( VEGF ), causes potentially fatal brain inflammation in certain patients.

Reseachers mimicked the drug’s activity in mice and found that it damaged the cell lining that prevents fluid from leaking from the ventricle into the brain.
The ventricle is the structure in the brain that holds cerebral spinal fluid after it is produced and which is continuous with the spinal cord.

The results are published in The Journal of Experimental Medicine.

“ This finding is significant because it may ultimately modify the way we use systemic drugs that block blood vessel growth, and it also suggests that VEGF ( vascular endothelial growth factor ) plays a more extensive role in the body than we previously thought, ” says Patricia D’Amore, at Schepens Eye Research Institute and principal investigator of the study.

Avastin inhibits the growth of tumors by cutting off their blood supply and thus depriving them of oxygen and other nutrients.
In a small percentage of patients, however, Avastin can cause neurological side effects, ranging from headaches and blurry vision to potentially fatal seizures and brain swelling.

D’Amore and her team found that VEGF normally protects the specialized cells that create a seal between the brain and ventricle and thus prevent fluid from leaking into the brain. When VEGF was blocked in mice, these cells were damaged and the animals developed brain lesions.
The authors suspect that Avastin’s side effects in humans may be caused by a similar phenomenon. Why these symptoms occur in only a few patients is not yet known.

Source: Schepens Eye Research Institute, 2008