Synthetic peptide outlasts macular degeneration med Eylea in animal models

Neovascular age-related macular degeneration is treated with frequent injections of drugs into the eye. Image: Tmhlee CC BY-SA 3.0

Neovascular, or “wet,” age-related macular degeneration is generally treated with a drug injected into the eyes. Johns Hopkins researchers have landed on a synthetic peptide with effects lasting twice as long as the drug’s, representing a potentially preferable alternative for patients.

Macular degeneration, considered incurable, refers to the deterioration of the macula, an area near the center of the retina. While the exact causes of the disease are unknown, neovascular AMD causes central vision loss from abnormal blood vessel growth in the eye, which, if left unchecked, may cause irreversible blindness.

Wet AMD is treated with anti-VEGF (vascular endothelial growth factor) drugs, such as Regeneron’s Eylea, via intraocular injection. The drugs help prevent the growth of leaky blood vessels in the eye that cause wet AMD's signature scarring and death of photoreceptors.

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While anti-VEGF injection is the most effective clinical treatment for wet AMD, its invasive nature can make it unattractive for patients. In fact, the Johns Hopkins team noted that the need for frequent eye injections is a "barrier to good outcomes."

The researchers, led by Raquel Lima e Silva, found that the synthetic peptide AXT107 halted the inappropriate blood vessel growth and curbed blood vessel leakage in two different mouse models of wet AMD. In rabbit eyes, the peptide cut leakage by 86% one month following injection and by 70% at the two-month mark.

In contrast, they found Eylea to reduce leakage by 69% at one month, and not at all at two months, showing that AXT107 may be effective over a longer period of time. The peptide collects as a gel in the eye, which may account for its staying power.

The researchers also found that a combination of AXT107 and Eylea suppressed subretinal blood vessel growth better than either treatment alone. Unlike Eylea, which targets VEGF, AXT107 interferes with three signaling pathways underlying blood vessel growth: VEGFR2, c-Met and PDGFRβ.

Although drugs like Eylea have been widely embraced in the fight against AMD, the search continues for more effective treatments. In August, scientists from Case Western Reserve University found that a combination of FDA-approved drugs protected mice from retinal damage, and they are planning clinical tests of the combo in macular degeneration and Stargardt disease. Meanwhile, the FDA approved VisionCare Ophthalmic Technologies’ implantable telescope for patients with bilateral, end-stage, AMD who are 65 or older.

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