Vector-based gene therapy shows efficacy treating glaucoma.
Gene therapy is a novel and promising approach that replaces faulty genes to treat a variety of conditions, including cancer.
Although glaucoma can be managed with standard treatments, researchers have tried to apply gene therapy techniques to treat the condition; however, they have had difficulty delivering the normal gene into cells that control fluid pressure in the eye.
Without the effective delivery of this gene, pressure and fluid build-up in the eye will continue among patients with glaucoma.
In a study published by Investigative Ophthalmology and Visual Science, the authors evaluated a new approach to delivering the gene to the trabecular meshwork and found it to be more effective than previous strategies.
“Most glaucoma can be treated with daily drug treatment," said researcher Paul Kaufman, MD. "Replacement genes could, theoretically, restore normal fluid flow for years on end, without requiring daily self-administration of eye drops that is inconvenient and may have local or even systemic side effects."
The researchers had been testing a vector for gene delivery based on feline immunodeficiency virus (FIV), which inserts genes into host DNA, according to the study. The authors noted that the eye initially protected against FIV and prevented gene delivery.
Once the virus penetrates a cell and sheds its membrane, defensive molecules from the host can "drag the virus particle to the cell's garbage disposal, called the proteasome, where it is degraded," Dr Brandt said. "We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery."
The authors started by marking FIV with a protein and placed the virus on cells of the trabecular meshwork.
The investigational gene therapy was observed to double the transfer of genes entering the cells, according to the study. The new genes also spread evenly across the trabecular meshwork.
The authors hypothesize that delivering additional copies of the gene will have a greater effect and further open the meshwork drain, thus reducing eye pressure, according to the study.
Although the current study identifies the best approach to transferring genes, the researchers have already identified at least 2 genes that could be used to reduce fluid build-up.
The authors noted that the vector-based gene therapy is likely harmless because they remove the virus’ genes prior to injection. Additionally, the effect on the anti-viral defense in the eye is temporary, according to the study.
“You encounter the drug once, then it is metabolized, and the innate inhibition is lost," Dr Brandt said.
The authors said that additional preclinical studies are necessary to establish the efficacy of the gene therapy approach before advancing to human trials.
"We have shown that this strategy does work in eye organ culture," Dr Brandt said. "Once we do further work on efficiency and identify which gene to deliver, then we are probably ready to move toward clinical trials."