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James Wawrzynski, Paul Gissen, Richard Bowman, Rebecca Bower, Chin Gan, Louise Harding, Amanda Mortensen, Dorothy Thompson, Robert Henderson; Intravitreal Cerliponase alfa for the treatment of CLN2 type Batten Disease related retinal dystrophy: A first in man report of ocular enzyme replacement. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1109.
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CLN2 type Batten Disease is a fatal neurodegenerative condition of childhood that is associated with retinal dystrophy and blindness. Intracerebroventricular infusion of Cerliponase alfa (rhTPP1) greatly slows the rate of neurodegenerative decline but not retinopathy. In 2020 intravitreal administration of rhTPP1 was shown to slow retinal degeneration in a canine model of CLN2. We report on the first-in-man use of intravitreal rhTPP1 for the treatment of CLN2 type Batten Disease associated retinal dystrophy.
8 children (4 female) aged 5-9 with genetically and clinically confirmed CLN2 Batten Disease were prospectively enrolled. Patients were selected if they were currently in the retinal degenerative phase of the condition. Enrolled children are undergoing 8-weekly intravitreal injections of rhTPP1 (0.2mg in 0.05ml) into the right eye for a total of 12 to 18 months. The left eye is untreated and acts as a paired control.The primary outcome is safety based on the clinical detection of intraocular complications and in particular uveitis. A secondary outcome is central foveal thickness (CFT) and paracentral macular thickness (PMT) measured by spectral domain OCT (Heidelberg Spectralis Flex).
Participants have had between 2 and 4 intravitreal injections and 4-6 months of followup so far. No adverse reactions (uveitis, raised IOP or media opacity) have been detected. The mean baseline CFT was 81µm (right), 87µm (left). The CFT has reduced by 16% in right eyes and 20% in left eyes. The mean baseline PMT was 213µm (right), 213µm (left). The PMT has reduced by 4% (right) and 7% (left).A paired t-test showed that the difference between the rate of foveal and paracentral retinal thinning between left and right eyes was not statistically significant (p= <0.05) at this early stage in the trial.A statistically significant difference between the PMT over time (but not CFT) was found for both right (p=0.046) and left (p=0.015) eyes (paired t-test).
Intravitreal rhTPP1 appears safe with no evidence of uveitis detected. Rapid retinal thinning is seen in untreated eyes, confirming that patients are in the degenerative phase of the condition. A slower rate of retinal thinning is seen in treated eyes, although a statistically significant difference is not seen at this early stage in the trial.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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