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NIH awards Phylonix phase II SBIR to develop zebrafish models for eye diseases

Cambridge, MA October 2, 2007 Phylonix Pharmaceuticals, Inc. today announced that it has been awarded a $1,092,031 Phase II Small Business Innovation Grant (SBIR) from the National Eye Institute of the National Institutes of Health (NIH) to develop zebrafish eye disease models for drug screening. The grant for New Models for Eye Diseases will support the Phylonix program over a period of three years.

The eye is a highly conserved organ and the basic structure between human and zebrafish eyes is indistinguishable. In addition, numerous eye diseases have been modeled in zebrafish including choroidal neovascularization, similar to age-related macular degeneration (AMD) in humans; ocular scarring that occurs after surgery for glaucoma; retinopathy induced by diabetes and edema; and ocular ischemia caused by several pathologies.

The funding for this program will be used to further develop our novel, patent pending methods for modeling eye diseases and to identify potential drug candidates, commented Patricia McGrath, Phylonix President and Chief Executive Officer. Our preliminary data show good correlation between results in zebrafish and results in mammals and we are very pleased to receive this Phase II SBIR award from the National Eye Institute.

Phylonix is modeling a number of eye diseases in zebrafish including diabetic retinopathy and AMD, the two leading causes of blindness in adults in the industrialized world. Both conditions involve vascular abnormalities, proliferation and leakage of new blood vessels. Other eye diseases resulting in blindness that Phylonix is modeling in zebrafish include retinopathy of prematurity, a major cause of newborn blindness in premature infants maintained by oxygen supplementation during the postnatal period. This disease involves intense neovascularization of the retina and leads to retinal detachment. Another cause of blindness is corneal neovascularization, which often results from injury and infection in the cornea.

Current mammalian models for ocular neovascularization require lengthy, tedious surgical manipulation and do not always result in improved vision; an alternative rapid, less invasive animal model for studying the process of ocular neovascularization and assessing drug effects will facilitate identification of new therapeutics. As the population ages, the incidence of eye diseases is rapidly increasing and convenient methods for assessing single and combination therapies in whole animals are urgently needed.

Advantages of using zebrafish for compound screening

Laboratory animals are critical for defining the mechanisms of drug activity and for testing therapeutic regimens, however, only a few useful models have been developed. Zebrafish has several important advantages for drug screening: they are small, inexpensive to maintain, and easily bred in large numbers. Zebrafish eggs are externally fertilized and a single mating produces 100-200 eggs. Single embryos can be maintained in fluid volumes as small as 100 microliters for the first six days of development and cultured in microtiter wells. Chemicals can then be added directly to the fish water, permeating the intact embryos. Standard microtiter plate readers can be used for quantitation, making this format particularly attractive for high-throughput drug screening.

Phylonix is developing a family of zebrafish assays with compelling advantages: 1) short assay time, 2) single dosing, 3) small amount of drug required for each test, 4) statistically significant numbers of animals can be assayed for each condition, 5) embryos maintenance during drug delivery is easy, and 6) low cost the estimated cost of each zebrafish assay is less than $100. Chemicals, small molecules, proteins, and nucleic acids such as knock-down reagents can be assessed using the Phylonix zebrafish assays.


Contact: Edward O'Lear

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