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Eyedrop Therapy

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Posted October 21, 2015

A research team led by scientists at Harvard Medical School, Beth Israel Deaconess Medical Center and the University of New Mexico School of Medicine has identified a small molecule that treats animal models of aged macular degeneration (AMD) and retinopathy of prematurity (ROP) by preventing the overgrowth of blood vessels that are characteristic of these two retinal diseases.

Image credit: National Eye Institute, NIH

Image credit: National Eye Institute, NIH

The new findings, described in the journal Science Translational Medicine, show that this molecule, named Vasotide in this paper, can be delivered in the form of eyedrops, a discovery that offers a promising alternative to current therapies for these retinal diseases, which require monthly injections of large molecules directly into the eyeball.

“Angiogenesis, the abnormal overgrowth of blood vessels, underlies many severe diseases, and when angiogenesis develops in the eye’s retina it causes decreased vision and can even lead to blindness,” said the study’s corresponding author Richard Sidman, the HMS Bullard Professor of Neuropathology, Emeritus, and an investigator in the Department of Neurology at Beth Israel Deaconess.

AMD develops in approximately 14 million older individuals throughout the U.S. This overgrowth of blood vessels damages the photoreceptor cells near the center of the eye’s retina, resulting in the loss of central vision so that individuals can no longer see objects directly in front of them. Retinopathy of prematurity (ROP) occurs in premature infants, who develop a similar retinal disease as a side effect of the high-level oxygen treatments used until their lungs develop sufficiently to handle the much lower oxygen levels in room air.

In previous investigations, the study’s co-senior authors Renata Pasqualini and Wadih Arap of the University of New Mexico School of Medicine, had developed a laboratory screening technique called in vivo phage display and used it to identify an early version of this peptide.

In this new study, Sidman and his co-authors tested Vasotide in three separate animal models—two forms of AMD and one form of ROP. Their results showed that Vasotide led to decreased blood vessel growth in all three models when the agent was administered by either systemic injection or through eyedrops.

“Under normal circumstances, a protein called vascular endothelial growth factor (VEGF) binds to pertinent endothelial cell receptors lining the blood vessels, causing these cells to multiply, migrate and form new blood vessels,” he noted. “Vasotide is the only external agent that uniquely blocks VEGF from binding to two different endothelial receptor molecules—VEGF receptor-1 and neuropilin-1—to keep excessive blood vessels from forming.”

Although a few other anti-VEGF drugs have been approved for therapy of AMD, they must be delivered directly into the eye through monthly intravitreal injections. “These treatments are costly, require highly skilled professional execution, and, in rare cases, can cause bleeding or infection in the eye,” said Sidman. Furthermore, he added, not all patients respond to these agents and, for many patients, responsiveness decreases after about six months.

“In addition to future clinical trials on AMD and ROP, we think that diabetic retinopathy and certain forms of cancer may also prove to be responsive to Vasotide,” said Sidman.

“This is a very exciting development in that it has the potential to allow the self-administration of a sight-saving drug to patients with AMD,” said Harold Dvorak, the HMS Mallinckrodt Distinguished Professor of Pathology at Beth Israel Deaconess, whose laboratory first identified the VEGF signaling protein nearly 30 years ago.

Source: HMS

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