Gene therapy proves effective in treating blindness

Gene therapy proves effective in treating blindness

Researchers from the Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia have conducted a recent study, published in Science Translational Medicine which focuses on gene therapy for congenital blindness. The scientists were able to improve sight in 3 adult patients who had previously been treated in one eye. The researchers used the same treatment on the second eye of the patients, and they were able to see in low-light situations and also find their way around. There were no conflicting effects reported.

The scientists report that the first and second treatments had no immune reactions which cancelled the genes administered. This has happened in previous studies of gene therapy on different diseases. This study in particular focused on addressing Leber congenital amaurosis (LCA), a retinal disease that results in complete loss of vision by the time the person is an adult.

Jean Bennett, M.D., Ph.D, F.M Kirby, professor of Ophthalmology at Penn., said:

"Patients have told us how their lives have changed since receiving gene therapy. They are able to walk around at night, go shopping for groceries and recognize people's faces - all things they couldn't do before. At the same time, we were able to objectively measure improvements in light sensitivity, side vision, and other visual functions."

During their research, researchers used neuroimaging to flash a dimly blinking checkerboard pattern in front of the patient's eye which had recently been treated. They found that a part of the brain responsible for vision brightened as a result of the functional magnetic resonance imaging (MRI).

Manzar Ashtari, Ph.D., of The Children's Hospital of Philadelphia, and the co-leader of the study says:

"This finding is telling us that the brain is responding to the eye's sensitivity to dim light".

The team administered patients with a vector, a genetically engineered adeno-associated virus, which was carrying a normal version of the gene named RPE65, which is mutated in one form of LCA. LCA is an accumulation of hereditary retinal diseases, in which a gene mutation challenges production of an enzyme necessary for light receptors in the retina.

Before this study, the researchers conducted a trial in Octorber of 2009, using the same gene therapy. The study involved 12 volunteers with LCA. Four of these patients were under the age of 11 when they were treated for the blindness. They only treated one eye in the patients - whichever eye was able to see better, and the study had evident results - 6 patients were able to see better, and were no longer considered "legally blind". Even though the testing on animals proved that re-administering the treatment in the second eye was safe, the researchers were skeptical that the vector in the eye which had not been treated could possibly result in inflammatory responses that could take away the benefits from the eye that wasn't treated.

The eye is somewhat separate from the body's immune system, therefore the concern was not high in terms of the inflammatory responses, however, further testing needed to be done in practice.

Bennett commented:

"Our concern was that the first treatment might cause a vaccine-like immune response that could prime the individual's immune system to react against a repeat exposure."

Like the first study, Albert M. Maguire, M.D, a study co-author, and professor of Opthalmology at Penn, administered the vector in the eye which was untreated previously, in 3 patients at The Children's Hospital of Philadelphia. These patients had received treatment 3 years prior. The authors then proceeded to observe the patients for 6 months after they had been readministered with the vector. The greatest advancements were in terms of light sensitivity, including the pupil's acknowledgments to light when it was seen in a range of different intensities. Out of the 3 patients, 2 were able to find their way through an obstacle course in very low-light situations.

The study showed no significant problems, and they actually discovered something they were not looking for. The fMRI findings demonstrated improvement in brain responses in the first treated eye, not just the newly treated one. The researchers say this is probably because the eyes were able to parallel each other in zooming in on the objects they were trying to see.

The authors say that it is important for further research to be done in order to ensure that gene therapy is an effective and safe way to treat retinal disease in humans.

Bennett concludes:

"However, the findings bode well for treating the second eye in the remaining patients from the first trial - including children, who may have better results because their retinas have not degenerated as much as those of the adults. What's more, the research holds promise for using a similar gene therapy approach for other retinal diseases."

The Children's Hospital of Philadelphia and The Center for Cellular and Molecular Therapeutics (CCMT) sponsored both trials and constructed the vector which carried the corrective gene. The director of CCMT, Katherine A. High, M.D., and pioneering gene therapy researcher, was the co-author of both studies.

CCMT, the Foundation Fighting Blindness, the National Institutes of Health, Research to Prevent Blindness, Hope for Vision, the Paul and Evanina Mackall Foundation Trust at the Scheie Eye Institute, the F.M Kirby Foundation, and anonymous donors funded this study.

Gene Therapy Explained (Video Medical And Professional 2020).

Section Issues On Medicine: Disease