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A cure for blindness is now a step closer

10.02.2012

By Adrian Galbreth

One of the main focuses of researchers around the world is how to combat visual decline, with experts on every continent striving to find a cure for blindness.

Now, thanks to experts in the US, it appears that we may be a step closer to therapies that can help to restore sight in those losing their vision.

Scientists from The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania have revealed that they have further improved vision in three adult patients previously treated in one eye using gene therapy.

The study, published in the journal Science Translational Medicine, reveals that after receiving the same treatment in their other eye, the patients became better able to see in dim light, and two were able to navigate obstacles in low-light situations, while no adverse effects occurred.

According to the specialists, neither the first treatment nor the re-administered treatment triggered an immune reaction that cancelled the benefits of the inserted genes, which had previously occurred in human trials of gene therapy for other diseases.

The researchers chose to target Leber congenital amaurosis (LCA), a retinal disease that progresses to total blindness by adulthood, explained study co-leader Dr Jean Bennett, the Kirby professor of Ophthalmology at Penn.

He noted that patients have explained how their lives have changed since receiving gene therapy.

"They are able to walk around at night, go shopping for groceries and recognise 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," he added.

Radiology researcher Dr Manzar Ashtari, from The Children's Hospital of Philadelphia, who was the study's co-leader, added that other objective results came from brain signals seen in neuroimaging.

He explained that when a dimly flickering checkerboard pattern flashed in front of a patient's recently treated eye, an area in the brain responsible for vision lit up during functional magnetic resonance imaging (fMRI).

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

In the first trial in October 2009, the study team injected LCA patients with a genetically engineered adeno-associated virus, which carried a normal version of a gene called RPE65 that is mutated in one form of LCA, and carried out a clinical trial of the gene therapy in 12 patients, four of them children aged 11 and younger, when they were treated.

Experts treated only one eye - the one with worse vision - and achieved sustained and notable results, with six subjects improving enough to no longer be classified as legally blind.

The team's experiments had showed that re-administering treatment in a second eye was safe and effective but, although the results were encouraging, the researchers were concerned that re-administering the vector in the untreated eye of the patients could stimulate an inflammatory response that would reduce the initial benefits in the untreated eye.

Dr Bennett noted that the main 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.

As the eye is relatively isolated from the body's immune system, such a response was considered less likely than in other parts of the body, but the idea needed to be tested in practice, she stated.

As with the initial study, retina specialist Dr Albert M Maguire, a study co-author, injected the vector into the untreated eyes of the three subjects at The Children's Hospital of Philadelphia, who had each been treated one and a half to three years before.

After following the three patients for six months after re-administration, the experts found the most significant improvements were in light sensitivity, such as the pupil's response to light over a range of intensities.

Two of the subjects were able to navigate an obstacle course in dim light, as captured in videos that accompanied the published study, while there were no safety problems and no significant immune responses.

There was even an unexpected benefit, with the fMRI results showing improved brain responses not only in the newly injected eye, but in the first one as well, possibly because the eyes were better able to coordinate with each other in fixating on objects.

According to Dr Bennett, 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.ADNFCR-1853-ID-801290207-ADNFCR




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