A gene therapy developed by an interdisciplinary research team to treat a form of complete color blindness has proven to be safe and effective in principle.
Healthy version of the CNGA3 gene is inserted directly into the patient’s retina
A gene therapy developed by scientists and physicians from Tübingen and Munich to treat a form of complete color blindness has proven to be safe and effective in principle in a phase I / II clinical study at the University Hospital in Tübingen. The first gene therapy for an inherited eye disease in Germany is to be developed further until it is ready for use.
In about a third of achromatopsia patients, the defect is in the CNGA3 gene. A team from the Research Institute for Ophthalmology at the University Hospital in Tübingen and the Department of Pharmacy and Ophthalmology at the Ludwig Maximilians University in Munich developed a gene therapy treatment for this genetic defect. In gene therapy, the healthy version of the CNGA3 gene is introduced directly into the patient’s retina via a harmless virus. After a few weeks, the retinal cells can use the healthy version of the CNGA3 gene and form the corresponding intact protein, which is supposed to restore the function of the defective cones. The gene ferries used, adeno-associated viruses, were developed at the Ludwig Maximilians University in Munich by Professor Stylianos Michalakis and Professor Martin Biel.
Even better treatment success expected in the future
The first clinical study on this therapy in humans has now been completed at the University Eye Clinic in Tübingen. It is published in the trade magazine American Medical Association’s JAMA Ophthalmology released. In the study, the worse eye of nine achromatopsy patients aged 24 to 59 years was treated surgically at the university eye clinic in Tübingen by injecting the gene therapeutic agent under the retina. “Subsequently, the subjects had no drug-related health problems and their retinas showed no permanent changes,” reports Professor Dominik Fischer, head of the clinical trial. The main concern of this first clinical study was achieved that the treatment could be classified as safe. In terms of effectiveness, too, there is a clearly positive effect. The visual function of the patients has improved somewhat, both in terms of visual acuity and in contrast and color vision.
“The study that has now been carried out is an important first step and milestone towards curative therapy for achromatopsia, and we expect even better treatment successes in the future,” says Professor Bernd Wissinger from the Tübingen Research Institute for Ophthalmology, who, together with Professor Martin Biel from the Department of Pharmacy of the Ludwig-Maximilians-Universität München leads the RD-CURE overall project for the development of gene therapy for hereditary retinal diseases.
Carry out gene therapy for the best possible effect in childhood
For safety reasons, the nine patients treated were in adulthood and thus had a retina that was already more or less severely damaged. “In addition, the parts of the brain that process vision become increasingly less plastic in adulthood,” emphasizes Professor Marius Ueffing, director of the Research Institute for Ophthalmology. “Since the brain of those affected by achromatopsia has never learned to process color vision, this plasticity is a necessary prerequisite for converting the newly acquired color vision of the retina into a real visual impression.” Since the study has shown that the therapy is safe, it may be advisable in the future to treat those affected so early that high brain plasticity and a retina that has not yet been damaged can increase the success of the treatment.
According to the scientists, the new gene therapy should therefore be carried out in analogy to the recently approved gene therapy drug Luxturna in childhood in order to have the best possible effect. “Since the gene vectors used have proven to be safe, a follow-up study in pediatric CNGA3 patients is possible and useful,” explains Professor Stylianos Michalakis from the Department of Ophthalmology at the Ludwig Maximilians University in Munich.
Source:
Fischer, M.D., Michalakis, S., et al .: Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia – A Nonrandomized Controlled Trial. JAMA Ophthalmology, https://dx.doi.org/10.1001/jamaophthalmol.2020.1032
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