Canadian Scientists Work Towards Gene Therapies for Retinoschisis and Stargardt Disease
Report from the annual ARVO (Association for Research in Vision and Ophthalmology) meeting
May 2, 2011 - Stargardt disease is the most common form of inherited cone-rod dystrophy. Mutations in one gene, called ABCA4, cause Stargardt disease and other cone-rod dystrophies by causing toxic materials to accumulate in retinal cells (the retinal pigment epithelium). These toxins cause the photoreceptors to fail. Dr. Robert Molday, a molecular biologist at the University of British Columbia, is leading the effort to develop therapies for this disorder.
For the past two years, Dr. Molday has led an international team of scientists working to develop gene therapies for retinal degenerative disorders, with an initial focus on the Stargardt gene. This team is funded by the Foundation Fighting Blindness and the Canadian Institutes of Health Research. With support from your donations, his work is helping to explain how mutations in the ABCA4 gene damage the photoreceptors and cause vision loss.
At this year’s ARVO conference Dr. Molday and a colleague, Dr. Marinko Sarunic of Simon Fraser University, report on their progress towards developing ABCA4 gene-replacement therapy in mice that have a defective ABCA4 gene.
To track the disease and its response to therapy, the researchers needed non-invasive ways of determining whether the newly developed treatments are effective. They developed new techniques for looking at the retina and the toxin deposits in the RPE of in the intact, living eye of these mice, called scanning laser ophthalmoscopy (SLO) and fluorescence imaging. Then they showed that increases in the intensity of the glow given off by deposits of toxin reflect increasing disease-related damage to the eye, and that a reduction in this glow represents improvements. This technique will be useful for measuring the effectiveness of new therapies in human clinical trials.
Dr. Molday has also been developing gene therapy for the most common form of X-linked retinoschisis which is due to mutations in the RS1 gene in over 95% of cases. At this year’s ARVO meeting, Dr. Molday and his colleagues report that they have successfully replaced this gene in the eyes of mice, giving affected retinal cells the normally functioning RSI gene that they need. As with the studies of Stargardt disease in mice, this work is paving the way to human clinical trials in the foreseeable future.
ARVO Presentations
Comparative Quantification Of Lipofuscin Deposits In the ABCA4 Knock Out Mouse Model Of STGD1 Utilizing Fluorescence Confocal Scanning Laser Ophthalmoscopy And Fourier Domain Optical Coherence Tomography. Presented Monday May 2, 2011. Lukasz Szczygiel, Ali Issaei, Nima Hossein-Javaheri, Laurie L. Molday, Robert S. Molday, Marinko V. Sarunic. Simon Fraser University, Burnaby; University of British Columbia, Vancouver.
AAV Variant-mediated Delivery of Retinoschisin Via Intravitreal Injection for Treatment of X-linked Retinoschisis. Presented Monday May 2, 2011.John G. Flannery, Leah Byrne, Meike Visel, Trevor Lee, Ryan R. Klimczak, William W. Hauswirth, Bernhard H. Weber, Robert S. Molday.University of California, Berkeley, CA; University of Florida; University of Regensburg, Germany; University of British Columbia, Vancouver.