Gene Therapy for Inherited Eye Diseases

Gene therapy for inherited eye diseases is a rapidly growing area of research and development that has seen some success. The first gene therapy approved to treat a blinding eye disease was Luxturna approved by the FDA in 2017 for the treatment of Leber congenital amaurosis (LCA), an inherited eye disease that affects the retina.

People born with LCA usually have severe visual impairment that begins in infancy that progresses during the early teenage years resulting in progressively reduced vision and then blindness because of gene mutations. One of the mutated genes that can cause LCA is RPE65 and that is the gene that Luxturna targets.

Viral Vector AAV

Luxturna works like this—The RPE65 gene is encased in a virus and injected into the eye under the retina and the gene enters the retinal cells and enables them to produce the missing enzyme called all-trans retinyl isomerase, which is necessary for the normal functioning of retinal cells.

The RPE65 gene is packaged into a harmless virus called adeno-associated virus (AAV). This type of virus will not cause disease because it has been modified so it no longer carries a disease-causing agent. The AAV is then used as a “viral vector” to deliver genetic material into cells.

Why are Viruses Used as Vectors in Gene Therapy

Viruses are used because they have evolved specifically to attach to receptor sites on the host cell membranes that allow them to gain access to the cells. Virus vectors can deliver the genetic material by doing what they evolved to do — “infecting” the nucleus of a cell.  But this type of “infecting a cell nucleus” is controlled and the virus only delivers the genetic material and not an infectious disease.  

Nearly all gene therapies currently available use one of three viral vector types: adeno-associated-virus (AAV) vectors, adenovirus vectors, or lentivirus vectors.

Additional methods of packaging genetic material for delivery into the body are being investigated. They include nanoparticles, encapsulating lipid molecules, and electric currents.

The Role of Genes

The human body has trillions of cells and within those cells are thousands of short sections of DNA that provide the information for the production of functional protein molecules 

Those small DNA sections that code for proteins are genes. A gene encodes protein and proteins determine cell function.

Enzymes are another type of protein that are created by genes. Enzymes are an essential part of the chemical processes of the body. They build muscle, destroy toxins, enable nerve functions, and break down food during digestion.

Current Inherited Eye Disease Gene Therapy Research

Today, five years after the first inherited eye disease gene therapy for Leber congenital amaurosis (LCA), there are more than 50 clinical trials for inherited eye diseases. Many new gene therapies are being studied for different types of vision loss such as for macular degeneration—both the neovascular (wet) and geographic atrophy (advanced dry form), and for diabetic macular edema, retinitis pigmentosa, Stargardt disease, achromatopsia (color blindness), Usher syndrome, and others.

Gene therapy only works if there are enough healthy retinal cells into which a new gene can be introduced. For cases of vision loss in which there are not enough healthy retinal cells for gene therapy, other novel therapies such as stem cell treatment or artificial retinas may hold the promise of restoring vision.

There are many challenges to successful gene therapy treatments for blinding eye diseases, one of which is that the exact gene mutation must be identified so that that specific gene can be altered, but despite this challenge, it is truly a revolutionary and promising time in the treatment of inherited retinal diseases.




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Gregory Scimeca, M.D.
Ophthalmologist and Medical Director
The Eye Professionals

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