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VEGF Neutralization Can Damage Brain Vessels, Say Schepens Eye Research Institute Scientists

Thursday, February 14, 2008 General News J E 4
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BOSTON, Feb. 13 New research by scientists at Schepens EyeResearch Institute may help explain why the anti-cancer drug Avastin, whichtargets a growth factor responsible for creation of new blood vessels, causespotentially fatal brain inflammation in certain patients. Institute scientistsmimicked the drug's activity in mice and found that it damaged the cell liningthat prevents fluid from leaking from the ventricle into the brain. Theventricle is the structure in the brain that holds cerebral spinal fluid afterit is produced and which is continuous with the spinal cord. The results arecurrently published online (on February 11th) in The Journal of ExperimentalMedicine.

"This finding is significant because it may ultimately modify the way weuse systemic drugs that block blood vessel growth, and it also suggests thatVEGF (vascular endothelial growth factor) plays a more extensive role in thebody than we previously thought," says Dr. Patricia D'Amore, senior scientistat Schepens Eye Research Institute and principal investigator of the study.

The cancer drug Avastin (bevacizumab) is used to treat advanced bowelcancer in combination with chemotherapy. By targeting VEGF, Avastin inhibitsthe growth of tumors by cutting off their blood supply and thus depriving themof oxygen and other nutrients. In a small percentage of patients, however,Avastin can cause neurological side effects, ranging from headaches and blurryvision to potentially fatal seizures and brain swelling.

D'Amore and her team found that VEGF normally protects the specializedcells that create a seal between the brain and ventricle and thus preventfluid from leaking into the brain. When VEGF was blocked in mice, these cellswere damaged and the animals developed brain lesions. The authors suspect thatAvastin's side effects in humans may be caused by a similar phenomenon. Whythese symptoms occur in only a few patients is not yet known.

Authors of the study include: Arindel S.R. Maharaj(2,3), Tony E.Walshe(2,3), Magali Saint-Geniez(2,3), Shivalingappa Venkatesha(2,4), Angel E.Maldonado (2,3), Nathan C. Himes(2), Kabir S. Matharu(3), S. AnanthKarumanchi(2,4) and Patricia A. D'Amore(1,2,3)

Schepens Eye Research Institute is an affiliate of Harvard Medical Schooland the largest independent eye research institute in the nation.(1) Departments of Ophthalmology and Pathology (2) Harvard Medical School (3) Schepens Eye Research Institute (4) Center for Vascular Biology, Departments of Medicine, Obstetrics, Gynecology, Surgery and Pathology, Beth Israel Deaconess Medical Center.

SOURCE Schepens Eye Research Institute
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