Advance In Glaucoma Gene Therapy

An improved tactic for the delivery of new genes into the eye’s trabecular meshwork fluid drain are being tested that could lead to a treatment to glaucoma at the University of Wisconsin-Madison.

Glaucoma is one of the leading and most common blinding diseases. The cause of glaucoma is excess pressure inside the eye, typically due to a clog in the fluid drain. Most cases are treatable with daily self administered treatments which may have local or systemic side effects.

While testing the scientist had issues getting efficient gene delivery to the cells that act as a drain to control the fluid pressure in the eye. The stumbling stone is that genes are not able to work until they actually enter a cell. Replacement genes could restore normal fluid flow without the need for daily self administration of drops. This study as published in the scientific journal Investigative Ophthalmology and Visual Science suggests an improved delivery tactic.

The team has been testing a vector based on FIV to deliver the genes. Much like the related human immunodeficiency virus, feline immunodeficiency virus can insert genes into the host DNA, the eye’s defense against FIV interfered with the delivery. Virus particles contain genes that are wrapped in a protein coat and a lipid membrane, after it enters the cell and sheds its membrane defensive host molecules drag the virus particle to be degraded at the proteasome. Scientists blocked the proteasome to see if it would prevent the destruction of the gene delivery and enhance the delivery method using FIV virus carrying a marker protein being placed on cells within the trabecular meshwork with or without a chemical that blocks proteasome. To prevent the forestall danger from injecting a virus, the genes are modified to remove all of the harmful genes so it has no chance to replicate and spread from where it is injected initially.

At a dosage above threshold the treatment doubled the transfer of genes that entered into the target cells. The newly introduced genes spread in a more uniform manner across the meshwork tissue, delivering more copies of the gene, having a greater therapeutic effect, opening the meshwork drain reducing pressure inside the eye. The current study concerns tools used for transferring genes, not the actual genes themselves, but at least 2 genes have been identified that could unplug the drain.

This technique does interfere with the antiviral eye defenses, but the effect is only temporary, once encountered the drug is metabolized and then the innate inhibition is lost. The strategy has been shown to work in eye organ cultures. With further work on efficiency and identifying which gene to deliver will make it ready for clinical trials.

Leber’s congenital amaurosis is a blinding eye disease that damages cell function that keeps light sensitive cells healthy, the replacement of the mutated genes has preserved and in some cases even improved vision in patients. This successful gene therapy is currently pending approval by the Food And Drug Administration.