Robert Koenekoop, MD, PhD

Secondary Axis: 
Research Focus: 

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.

blindness, gene therapy, novel gene discovery, whole genome studies, SNP genotyping, homozygosity mapping
Montreal Children's Hospital
Wang H, den Hollander AI, Moayedi Y, Abulimiti A, Li Y, Collin RW, Hoyng CB, Lopez I, Abboud EB, Al-Rajhi AA, Bray M, Lewis RA, Lupski JR, Mardon G, Koenekoop RK, Chen R. Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. Am J Hum Genet. 2009 Mar;84(3):380-7. Epub 2009 Mar 5. Erratum in: Am J Hum Genet. 2010 Feb;86(2):293.
Louie CM, Caridi G, Lopes VS, Brancati F, Kispert A, Lancaster MA, Schlossman AM, Otto EA, Leitges M, Gröne HJ, Lopez I, Gudiseva HV, O'Toole JF, Vallespin E, Ayyagari R, Ayuso C, Cremers FP, den Hollander AI, Koenekoop RK, Dallapiccola B, Ghiggeri GM, Hildebrandt F, Valente EM, Williams DS, Gleeson JG. AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat Genet. 2010 Feb;42(2):175-80. Epub 2010 Jan 17.
Khanna H, Davis EE, Murga-Zamalloa CA, Estrada-Cuzcano A, Lopez I, den Hollander AI, Zonneveld MN, Othman MI, Waseem N, Chakarova CF, Maubaret C, Diaz-Font A, Macdonald I, Muzny DM, Wheeler DA, Morgan M, Lewis LR, Logan CV, Tan PL, Beer MA, Inglehearn CF, Lewis RA, Jacobson SG, Bergmann C, Beales PL, Attié-Bitach T, Johnson CA, Otto EA, Bhattacharya SS, Hildebrandt F, Gibbs RA, Koenekoop RK, Swaroop A, Katsanis N. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat Genet. Jun;41(6):739-45. Epub 2009 May 10.

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