Interventions and Treatments: Clinical


Inherited retinal degenerations are currently not treatable with two exceptions: electronic chip implants which are approved for patients at a severe stage of disease with little remaining vision, and subretinal gene augmentation therapy for RPE65 form of Leber congenital amaurosis (LCA) . Our group has been involved in clinical trials evaluating potential treatments as well as mechanism-specific interventions designed to better understand pathophysiology of retinal disease.

Our ongoing clinical trial in GUCY2D-LCA is evaluating gene augmentation therapy. Initial results from the first cohort of three patients (220) and the hyperresponders from the last cohort (232) were reported.

We took part in an international multi-center clinical trial to evaluate intravitreal injections of an antisense oligonucleotide sepofarsen targeting a specific intronic mutation in CEP290-LCA. Preliminary results suggested improvement of vision (197). Recently we demonstrated that a single injection can result in substantial improvements of day vision at the foveal cones with an unexpected durability of more than 15 months (219), details of improvements in patients with LP vision (227), and published the full trial results (229).

Our clinical trial in RPE65-LCA was a single center Phase I/II trial supported by the National Eye Institute. We performed subretinal gene therapy in 15 children and adults, and reported our wide ranging observations in the short and long term (97,98,104,106,109,122,129,133,143,146,148). In addition we collaborated in another subretinal gene therapy clinical trial in RPE65-LCA performed in Israel (111).

We have also taken part in a multi-center clinical trial funded by QLT to evaluate oral retinoid therapy in RPE65-LCA (146).

We have been involved in a multi-center clinical trial funded by Second Sight to evaluate Argus II electronic chip implants in patients with retinitis pigmentosa (125,150,165).

Previously, we evaluated the short-term consequences of high dose oral vitamin A in TIMP3-asssociated Sorsby fundus dystrophy, vitamin A deficiency and CTRP5- (also known as C1QTNF5) associated late-onset retinal degeneration (12,20,45).

In addition, we evaluated the short-term consequences of lutein supplementation in RP, Usher syndrome, choroideremia and ABCA4-associated Stargardt disease (44,50,81).

27 Publications On Clinical Interventions And Potential Treatments

232. Jacobson SG, CIDECIYAN AV, Ho AC, Roman AJ, Wu V, Garafalo AV, Sumaroka A, Krishnan AK, Swider M, Mascio AA, Kay CN, Yoon D, Fujita KP, Boye SL, Peshenko IV, Dizhoor AM, Boye SE. Night vision restored in days after decades of congenital blindness. iScience, 25:105274, 2022. [PubMed] [DOI]

229. Russell SR, Drack AV, CIDECIYAN AV, Jacobson SG, Leroy BP, Van Cauwenbergh C, Ho AC, Dumitrescu AV, Han IC, Martin M, Pfeifer WL, Sohn EH, Walshire J, Garafalo AV, Krishnan AK, Powers CA, Sumaroka A, Roman AJ, Vanhonsebrouck E, Jones E, Nerinckx F, De Zaeytijd J, Collin RWJ, Hoyng C, Adamson P, Cheetham ME, Schwartz MR, den Hollander W, Asmus F, Platenburg G, Rodman D, Girach A. Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: A Phase 1b/2 trial. Nature Medicine, 28:1014-1021, 2022. [PubMed] [DOI] 

227. CIDECIYAN AV, Jacobson SG, Ho AC, Krishnan AK, Roman AJ, Garafalo AV, Wu V, Swider M, Sumaroka A, Van Cauwenbergh C, Russell SR, Drack AV, Leroy BP, Schwartz MR, Girach A. Restoration of cone sensitivity to individuals with congenital photoreceptor blindness within the phase 1/2 sepofarsen trial. Ophthalmology Science, 2:100133, 2022. [PubMed] [DOI]

220. Jacobson SG, CIDECIYAN AV, Ho AC, Peshenko IV, Garafalo AV, Roman AJ, Sumaroka A, Wu V, Krishnan AK, Sheplock R, Boye SL, Dizhoor AM, Boye SE. Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations. iScience, 24, 102409, 2021. [PubMed] [DOI] [] [Penn Press Release]

219. CIDECIYAN AV, Jacobson SG, Ho AC, Garafalo AV, Roman AJ, Sumaroka A, Krishnan AK, Swider M, Schwartz MR, Girach A. Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report. Nature Medicine, 27:785-789, 2021. [PubMed] [DOI] [] [Penn Press Release]

197. 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] [] [UPenn Press Release] [ProQR Press Release] 

165. da Cruz L, Dorn JD, Humayun MS, Dagnelie G, Handa J, Barale P-O, Sahel J-A, Stanga PE, Hafezi F, Safran AB, Salzmann J, Santos A, Birch D, Spencer R, CIDECIYAN AV, de Juan E, Duncan JL, Eliott D, Fawzi A, de Koo LCO, Ho AC, Brown G, Haller J, Regillo C, Del Priore LV, Arditi A, Greenberg RJ, for the Argus II Study Group. Five-year safety and performance results from the Argus II retinal prosthesis system clinical trial. Ophthalmology 123:2248-2254, 2016. [PubMed]

150. Ho AC, Humayun MS, Dorn JD, et al., CIDECIYAN AV, et al., Arditi A, Geruschat DR, Greenberg RJ. Long-term results from an epiretinal prosthesis to restore sight to the blind. Ophthalmology 122:1547-54, 2015. [PubMed]

148. Jacobson SG, CIDECIYAN AV, Roman AJ, Sumaroka A, Schwartz SB, Heon E, Hauswirth WW. Improvement and decline in vision with gene therapy in childhood blindness. New England Journal of Medicine 372:1920-1926, 2015. [PubMed] [Editorial] [NEI Press Release] [Penn Press Release] [Science Now]

146. Jacobson SG, CIDECIYAN AV, Aguirre GD, Roman AJ, Sumaroka A, Hauswirth WW, Palczewski K. Improvement in vision: a new goal for treatment of hereditary retinal degenerations. Expert Opinion on Orphan Drugs 3:563-575, 2015. [PubMed]

143. CIDECIYAN AV, Aguirre GK, Jacobson SG, Butt OH, Schwartz SB, Swider M, Roman AJ, Sadigh S, Hauswirth WW. Pseudo-fovea formation after gene therapy for RPE65-LCA. Investigative Ophthalmology & Visual Science 56:526-537, 2015. [PubMed]

133. CIDECIYAN AV, Jacobson SG, Beltran WA, Hauswirth WW, Aguirre GD. Reply to Townes-Anderson: RPE65 gene therapy does not alter the natural history of retinal degeneration. Proceedings of the National Academy of Sciences USA 110:E1706, 2013. [PubMed]

129. CIDECIYAN AV, Jacobson SG, Beltran WA, Sumaroka A, Swider M, Iwabe S, Roman AJ, Olivares MB, Schwartz SB, Komaromy AM, Hauswirth WW, Aguirre GD. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proceedings of the National Academy of Sciences USA 110:E517-25, 2013. [PubMed] [NEI News Brief] [Penn News] [Commentary] [WOC Lecture] [PDF]

125. Humayun MS, Dorn JD, da Cruz L, Dagnelie G, Sahel J-A, Stanga PE, CIDECIYAN AV, Duncan JL, Eliott D, Filley E, Ho AC, Santos A, Safran AB, Arditi A, Del Priore LV, Greenberg RJ for the Argus II Study Group. Interim results from the international trial of Second Sight’s visual prosthesis. Ophthalmology 119:779-788, 2012.[PubMed]

122. Jacobson SG, CIDECIYAN AV, Ratnakaram R, Heon E, Schwartz SB, Roman AJ, Peden MC, Aleman TS, Boye SL, Sumaroka A, Conlon TJ, Calcedo R, Pang J-J, Erger KE, Olivares MB, Mullins CL, Swider M, Kaushal S, Feuer WJ, Iannaccone A, Fishman GA, Stone EM, Byrne BJ, Hauswirth WW. Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: Safety and efficacy in fifteen children and adults followed up to three years. Archives of Ophthalmology 130:9-24, 2012.[PubMed]

111. Banin E, Bandah-Rosenfeld D, Obolensky A, CIDECIYAN AV, Aleman TS, Marks-Ohana D, Sela M, Boye S, Sumaroka A, Roman AJ, Schwartz SB, Hauswirth WW, Jacobson SG, Sharon D. Molecular anthropology meets genetic medicine to treat blindness in the north african Jewish population: Human gene therapy initiated in Israel. Human Gene Therapy, 21:1749-1757, 2010. [PubMed]

109. CIDECIYAN AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Progress in Retinal and Eye Research, 29:398-427, 2010.[PubMed]

106. CIDECIYAN AV, Hauswirth WW, Aleman TS, Kaushal S, Schwartz SB, Boye SL, Windsor EAM, Conlon TJ, Sumaroka A, Pang J, Roman AJ, Byrne BJ, Jacobson SG. Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Human Gene Therapy, 20:999-1004, 2009.[PubMed] [Reprint]

104. CIDECIYAN AV, Hauswirth WW, Aleman TS, Kaushal S, Schwartz SB, Boye SL, Windsor EAM, Conlon TJ, Sumaroka A, Roman AJ, Byrne BJ, Jacobson SG. Vision 1 year after gene therapy for Leber’s congenital amaurosis. New England Journal of Medicine, 361:725-727, 2009. [PubMed] [Reprint] [Free Text in PubMed Central]

98. CIDECIYAN AV, Aleman TS, Boye SL, Schwartz SB, Kaushal S, Roman AJ, Pang J-j, Sumaroka A, Windsor EAM, Wilson JM, Flotte TR, Fishman GA, Heon E, Stone EM, Byrne BJ, Jacobson SG, Hauswirth WW. Human gene therapy for RPE65-isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proceedings of the National Academy of Sciences USA, 105: 15112-15117, 2008. [PubMed] [PDF]

97. Hauswirth WW, Aleman TS, Kaushal S, CIDECIYAN AV, Schwartz SB, Wang L, Conlon TJ, Boye SL, Flotte TR, Byrne BJ, Jacobson SG. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Human Gene Therapy 19:979-990, 2008. [PubMed]

81. Aleman TS, CIDECIYAN AV, Windsor EAM, Schwartz SB, Swider M, Chico JD, Sumaroka A, Pantelyat AY, Duncan KG, Gardner LM, Emmons JM, Steinberg JD, Stone EM, Jacobson SG. Macular pigment and lutein supplementation in ABCA4-associated retinal degenerations. Investigative Ophthalmology & Visual Science 48:1319-1329, 2007. [PubMed]

50. Duncan JL, Aleman TS, Gardner LM, De Castro E, Marks DA, Emmons JM, Bieber ML, Steinberg JD, Bennett J, Stone EM, Macdonald IM, CIDECIYAN AV, Maguire MG, Jacobson SG. Macular pigment and lutein supplementation in choroideremia. Experimental Eye Research 74:371-381, 2002. [PubMed]

45. Jacobson SG, CIDECIYAN AV, Wright E, Wright AF. Phenotypic marker for early disease detection in dominant late-onset retinal degeneration. Investigative Ophthalmology & Visual Science 42:1882-1890, 2001. [PubMed]

44. Aleman TS, Duncan JL, Bieber ML, de Castro E, Marks DA, Gardner LM, Steinberg JD, CIDECIYAN AV, Maguire MG, Jacobson SG. Macular pigment and lutein supplementation in retinitis pigmentosa and usher syndrome. Investigative Ophthalmology & Visual Science 42:1873-1881, 2001. [PubMed]

20. CIDECIYAN AV, Lamb TD, Pugh EN Jr, Huang Y, Jacobson SG. Rod plateaux during dark adaptation in Sorsby's fundus dystrophy and vitamin A deficiency. Investigative Ophthalmology & Visual Science 38:1786-1794, 1997. [PubMed]

12. Jacobson SG, CIDECIYAN AV, Regunath G, Rodriguez FJ, Vandenburgh K, Sheffield VC and Stone EM. Night blindness in a TIMP3-associated Sorsby's fundus dystrophy is reversed by vitamin A. Nature Genetics 11:27-32, 1995. [PubMed]

Last updated October 25, 2022