New Approach May Make Gene Therapy More Useful for Older Patients

April 19, 2013 - Scientists at Michigan State University have made a fascinating discovery that may make gene therapy for retinal eye diseases more effective, and therefore useful for more people.

Achromatopsia is an inherited form of total colour blindness, caused by damage in all kinds of cone photoreceptors. In this respect, it resembles Stargardt disease or cone-rod dystrophy. One form of achromatopsia is caused by a mutation in the CNGB3 gene, which is necessary for the function of all types of cones. This form of achromatopsia occurs not only in people, but also in some dogs, which can serve as a model for studying what causes it and how to treat it.

In previous work, veterinary ophthalmologist Dr. Andras Komáromy and his colleagues had treated dog with achromatopsia of this type. They found that they could restore vision to the dogs with gene therapy, replacing the defective gene with a normally functioning one. (See our video on gene therapies.) However, the treatment was really effective only if the animals were treated before reaching 1 year of age. This raises questions about the age at which humans could be successfully treated.

Dr. Komáromy’s team suspected that the failure of gene therapy in older dogs was due to the advanced stage of degeneration in cone photoreceptors, and so they decided on a strategy of making the damaged cones more receptive to repair before delivering the replacement genes. To do this, before delivering the replacement genes they pre-treated the dog’s eyes with an injection of ciliary neurotrophic factor (CNTF), a substance already known to make photoreceptors become less mature and priming them to re-grow their normal adult structures. Intraocular capsules that slowly release CNTF are currently being studied in clinical trials as a potential treatment for retinitis pigmentosa.

In the new studies, the efficacy of gene therapy for CNGB3-based achromatopsia in older dogs was remarkably improved by pre-treatment with CNTF. “It was a long shot,” said Komáromy. “We were just amazed at what we found. All seven dogs that got the combination treatment responded, regardless of age.”

This approach points the way to a new strategy that might allow humans with a variety of retinal diseases to be treated more effectively with gene-replacement therapies, even at an older age.  

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