Our group studies disease mechanisms in inherited retinal degenerations (IRDs), and evaluates efficacy and safety of potential treatments. IRDs result in vision loss due to mutations in more than 200 different genes and include diagnoses such as Retinitis Pigmentosa, Stargardt Disease, Leber Congenital Amarousis, and others. There are multitudes of different pathological mechanisms resulting from different mutations. Our group uses non-invasive tests to link changes in retinal structure and function to underlying molecular pathology. We also develop and evaluate novel outcome measures for use in clinical trials.
December 17, 2018: Positive results from clinical trial published in Nature Medicine
Vision is one of the most important senses for humans to negotiate their complex world. A blindness called Leber congenital amaurosis (LCA) results from mutations acting primarily either on the photoreceptors or on their support cells called RPE. Primary photoreceptor blindness is the most common form of LCA and it is currently not treatable, whereas RPE65 form of primary RPE blindness has been treated by gene therapy.
The most common form of photoreceptor blindness is due to CEP290 mutations which result in pathophysiology at the connecting cilium. The connecting cilium refers to the narrow intracellular link between light sensing antenna and the rest of the photoreceptor cells. An antisense oligonucleotide (AON) was designed to ameliorate this ciliopathy and increase the normal CEP290 protein levels in photoreceptors.
A Phase I/II clinical trial involving intravitreal injections of the AON has been ongoing at the Scheie Eye Institute of the Perelman School of Medicine, University of Pennsylvania since November 2017 in collaboration other centers in the US and Europe. Interim results suggest that the AON has an acceptable safety profile that treated eyes demonstrate significantly improved vision. Safety of the drug, and the efficacy and durability of the effect continue to be evaluated.
Cideciyan AV, Jacobson SG, Drack AV, Ho AC, Charng J, Garafalo AV, Roman AJ, Sumaroka A, Han IC, Hochstedler MD, Pfeifer WL, Sohn EH, Taiel M, Schwartz MR, Biasutto P, de Wit W, Cheetham ME, Adamson P, Rodman DM, Platenburg G, Tome MD, Balikova I, Nerinckx F, De Zaeytijd J, Van Cauwenbergh C, Leroy BP, Russell SR. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nature Medicine, 25:225-228, 2019. [PubMed] [Nat Med: News and Views] [Clinicaltrials.gov] [UPenn Press Release] [ProQR Press Release]
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