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Research

Study advances gene therapy for glaucoma

08/02/2018
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Scientists attempting to use gene therapy to reduce intraocular pressure have discovered an improved method for delivering genes to the trabecular meshwork.

The group of researchers from University of Wisconsin-Madison were attempting to develop a long-lasting treatment for glaucoma by using a vector based on feline immunodeficiency virus (FIV) to deliver the gene.

However, they had been frustrated by the eye’s innate ability to interfere with the delivery – after entering the eye, defensive molecules would drag the virus particle in to the proteasome, where it was degraded.

As a result, the researchers tried a new technique to try and overcome this issue.

“We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery,” explained study co-investigator Professor Curtis Brandt.

“We have shown that this strategy does work in eye organ culture. Once we do further work on efficiency and identify which gene to deliver, then we are probably ready to move toward clinical trials.”



"We have shown that this strategy does work in eye organ culture."
Professor Curtis Brandt, Study co-investigator

Brandt and his colleague, Professor Paul Kaufman, were able to track their experiment by placing markers on the FIV virus, which was placed on cells of the trabecular meshwork, both with and without a chemical that blocked proteasomes.

They found it roughly doubled the transfer of genes entering the target cells, while simultaneously spreading them more uniformly across the meshwork tissue. Theoretically, delivering more copies of the gene should give a greater therapeutic effect, opening the meshwork drain and reducing pressure inside the eye.

However, while successful, Brandt stressed the study concerned the tools for transferring genes, not the genes themselves. Despite this he said he and Kaufman had “already identified at least two genes that could unplug the drain.”

He also explained how the duo protected against the inherent danger of injecting a virus into the eye: “We take out pretty much all of the virus’ genes, so it has no chance to replicate and spread from where it’s initially injected.”

Also, according to Brandt, although the technique does interfere with the anti-viral defense in the eye, the effect is temporary.

“You encounter the drug once, then it is metabolised, and the innate inhibition is lost,” he said.

GLAUKOS
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The study was published in last month’s issue of Investigative Ophthalmology and Visual Science.

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