May 20, 2014
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Lentiviral vector may deliver sustained antiangiogenic therapy

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NEW YORK — Advances in gene therapies for ocular disease have reached a point where it may be possible for therapeutic effects to be sustained for years, Timothy Stout, MD, said in the Verhoeff Lecture at the American Ophthalmological Society meeting here.

To illustrate the advance, Stout recounted experiments underway in nonhuman primates in which the retina of the right eye was injected with plain saline, with a lentivirus that contained a marker gene, or with a lentivirus that contained two antiangiogenic genes — in this case, endostatin and angiostatin. Weeks later, both eyes underwent laser.

“In animals that received a subretinal injection of saline, there was no difference between the right eye and the left eye in terms of proclivity for developing subretinal neovascularization,” Stout said. Similarly there was no difference between eyes when a marker gene had been injected.

However, in eyes that received 1× or 10× antiangiogenic gene, there was a “remarkable inhibition” of neovascularization compared with the left eye, Stout said.

“This to us suggested that this treatment was perhaps effective in treating neovascularization,” Stout said. To determine whether the effect was sustained, the nonhuman primates underwent laser again 10 months later.

“We found the same thing,” Stout said. There was no difference between the left eye and the right eye in terms of development of subretinal neovascularization in animals that previously received the saline injection or the lentivirus marker gene injection, but there was a “persistent long-lived effect in terms of the inhibition of the neovascularization in the right eye” in the animals that had previously received the antiangiogenic genes.

“VEGF blockade for exudative AMD is effective but it’s cumbersome,” Stout said. “We have a number of antiangiogenic genes that might provide therapeutic effect, and we’ve demonstrated that long-term inhibition of subretinal neovascularization is possible using the lentivirus.”

Disclosure: Stout is a consultant for, speaker for, and has patent or royalty interest in Oxford BioMedica.