Robert Koenekoop, MD, PhD
Photoreceptors are modified cilia that provide vision through a complicated, genetically determined program. Death of these light-sensing photoreceptor cells causes irreversible blindness in inherited retinal degenerations (IRDs) such as Leber congenital amaurosis (LCA) at birth and retinitis pigmentosa (RP) and con-rod degenerations (CRD) during teenage years. IRDs are the most common cause of visual loss in the world and affect more than 16 million patients, at least 60,000 Canadians and 18,000 Quebecers. Genetic research has thusfar identified almost 200 retinal genes for IRDs, and these mutations explain 50% of patients. The goal of our genetic research program is to identify the remaining genes. Until this year, IRDs were thought to be incurable. This has been disproven in human clinical trials which showed that replacement of one LCA gene, RPE65, led to visual recovery, while for another LCA gene, LRAT, we showed at McGill, that pharmacological bypass of the blocked retinoid cycle recued visual acuity, visual field and cone photoreceptor function in the first three humans (confidential). These studies illustrate that our genotyping and gene discovery data quickly lead to human therapies for this devastating and progressive group of human blindness. It also illustrates the benefits of genotyping large cohorts of IRD patients, to classify them into those that can get treated right away and those that may be treated later. In the past three years we have been able to identify seven new genes (TOPORS1, CEP290, LCA5, EYS, PDE6C, SPATA7 and last month NPHP5) using a novel three step test. We will continue to search for new IRD genes, using these successful strategies.