Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy

Richard G. Weleber; Mark E. Pennesi; David J. Wilson; Shalesh Kaushal; Laura R. Erker; Lauren Jensen; Maureen T. McBride; Terence R. Flotte; Margaret Humphries; Roberto Calcedo; William W. Hauswirth; Jeffrey D. Chulay; J. Timothy Stout

doi:10.1016/j.ophtha.2016.03.003

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy

Richard G. Weleber, Mark E. Pennesi, David J. Wilson, Shalesh Kaushal, Laura R. Erker, Lauren Jensen, Maureen T. McBride, Terence R. Flotte, Margaret Humphries, Roberto Calcedo, William W. Hauswirth, Jeffrey D. Chulay, J. Timothy Stout

Ophthalmology

Research output: Contribution to journal › Article › peer-review

170 Scopus citations

Abstract

Purpose To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Design Nonrandomized, multicenter clinical trial. Participants Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Methods Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. Main Outcome Measures The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V₃₀) and total visual field hill of vision (V_TOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. Results All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V₃₀ increased in 6 patients, V_TOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Conclusions Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.

Original language	English (US)
Pages (from-to)	1606-1620
Number of pages	15
Journal	Ophthalmology
Volume	123
Issue number	7
DOIs	https://doi.org/10.1016/j.ophtha.2016.03.003
State	Published - Jul 1 2016

ASJC Scopus subject areas

Ophthalmology

Access to Document

10.1016/j.ophtha.2016.03.003

Cite this

Weleber, R. G., Pennesi, M. E., Wilson, D. J., Kaushal, S., Erker, L. R., Jensen, L., McBride, M. T., Flotte, T. R., Humphries, M., Calcedo, R., Hauswirth, W. W., Chulay, J. D., & Stout, J. T. (2016). Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy. Ophthalmology, 123(7), 1606-1620. https://doi.org/10.1016/j.ophtha.2016.03.003

Weleber, RG, Pennesi, ME, Wilson, DJ, Kaushal, S, Erker, LR, Jensen, L, McBride, MT, Flotte, TR, Humphries, M, Calcedo, R, Hauswirth, WW, Chulay, JD & Stout, JT 2016, 'Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy', Ophthalmology, vol. 123, no. 7, pp. 1606-1620. https://doi.org/10.1016/j.ophtha.2016.03.003

@article{a8e831f162e54601a5fb20d0e9dd7b7f,

title = "Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy",

abstract = "Purpose To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Design Nonrandomized, multicenter clinical trial. Participants Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Methods Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. Main Outcome Measures The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. Results All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Conclusions Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.",

author = "Weleber, {Richard G.} and Pennesi, {Mark E.} and Wilson, {David J.} and Shalesh Kaushal and Erker, {Laura R.} and Lauren Jensen and McBride, {Maureen T.} and Flotte, {Terence R.} and Margaret Humphries and Roberto Calcedo and Hauswirth, {William W.} and Chulay, {Jeffrey D.} and Stout, {J. Timothy}",

note = "Publisher Copyright: {\textcopyright} 2016 American Academy of Ophthalmology.",

year = "2016",

month = jul,

day = "1",

doi = "10.1016/j.ophtha.2016.03.003",

language = "English (US)",

volume = "123",

pages = "1606--1620",

journal = "Ophthalmology",

issn = "0161-6420",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy

AU - Weleber, Richard G.

AU - Pennesi, Mark E.

AU - Wilson, David J.

AU - Kaushal, Shalesh

AU - Erker, Laura R.

AU - Jensen, Lauren

AU - McBride, Maureen T.

AU - Flotte, Terence R.

AU - Humphries, Margaret

AU - Calcedo, Roberto

AU - Hauswirth, William W.

AU - Chulay, Jeffrey D.

AU - Stout, J. Timothy

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Purpose To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Design Nonrandomized, multicenter clinical trial. Participants Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Methods Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. Main Outcome Measures The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. Results All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Conclusions Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.

AB - Purpose To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Design Nonrandomized, multicenter clinical trial. Participants Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Methods Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. Main Outcome Measures The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. Results All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Conclusions Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.

UR - http://www.scopus.com/inward/record.url?scp=84963812408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963812408&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2016.03.003

DO - 10.1016/j.ophtha.2016.03.003

M3 - Article

C2 - 27102010

AN - SCOPUS:84963812408

SN - 0161-6420

VL - 123

SP - 1606

EP - 1620

JO - Ophthalmology

JF - Ophthalmology

IS - 7

ER -

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this