After gene therapy for congenital blindness, areas in the part of the brain responsible for vision show a response after a visual stimulus (Credit: The Children's Hospital of Philadelphia)

By Mariel Emrich, Columbia Grammar and Preparatory School

Gene therapy is one of the newest methods used to help treat diseases. Usually, the mutated gene gets replaced with a copy of the healthy gene. However, some diseases only require the mutated gene to be inactivated.

Gene therapy is risky because it can come with many side effects, including drop in blood pressure, nausea, or severe chills. These side effects occur because the new gene may be treated as a foreign substance by your body. Scientists do not know all of the possible side effects, since only a few have come up in clinical trials so far.

Recently, there was a study by scientists, including the co-leader Jean Bennet, and Manzar Ashtari from the Children’s Hospital of Philadelphia and from the Perelman School of Medicine at the University of Pennsylvania that was published in Science Translational Medicine. The study showed successful gene therapy for inherited blindness for patients who have been treated with gene therapy previously in one eye. The particular disease is called leber congenital amaurosis (LCA). LCA is a group of hereditary retinal diseases in which a gene mutation impairs production of an enzyme crucial to light receptors in the retina. The patients were injected with a vector, a genetically engineered adeno-associated virus, which carried a normal version of a gene called RPE65. After the gene therapy, patients were able to see in dim light, and two out of three were able to navigate obstacles in low-light situations.

Fortunately, there were no harmful side effects. The treatment did not trigger an immune reaction that cancel the benefits of the inserted genes, which is what has happened at gene therapy clinical trials in the past.

Patients have noted that after receiving gene therapy, they were able to walk around at night and recognize people’s faces, which they couldn’t do before. Neuroimaging also showed positive brain signals. A flickering checkerboard pattern flashed in front of a patient’s treated eye, an area in the brain responsible for vision lit up during functional magnetic resonance imaging (fMRI).

Before clinical trials, gene therapy for this disease was performed on animals. Treatment in a second eye was safe an effective in animals. However, researchers were concerned that in humans it might stimulate an inflammatory response that could reduce the initial benefits in the other eye. Once a gene gets put into a body, if it is re-injected the body may act immune to the substance, and cause an inflammatory response. The study showed that inserting the gene into the second eye was not a problem.

The research holds hope for using a gene approach to cure retinal diseases, particularly in children who may have better results because their retinas have not degenerated as much as those of the adults.

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Mariel is currently a sophomore at Columbia Grammar and Preparatory School in New York City. She loves learning about science and particularly enjoys genetics, cancer research, radiology, and forensics.