Intravitreal Cerliponase alfa slows the rate of retinal thinning in patients with CLN2 type Batten Disease: A first in man report.

Abstract

Purpose : 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 Cerliponase alfa was shown to slow retinal degeneration in a canine model of CLN2. We report a first-in-man compassionate use programme of intravitreal Cerliponase alfa for the treatment of CLN2 type Batten Disease associated retinal dystrophy.

Methods : 8 children aged 5-9 with genetically and clinically confirmed CLN2 Batten Disease were prospectively recruited. Our most severely affected patients were enrolled provided that they had some residual visual behaviours. The patients underwent 8-weekly intravitreal injections of rhTPP1 (0.2mg in 0.05ml) into the right eye for 12 to 18 months. The left eye was untreated and acts as a paired control.

The primary outcome was safety based on the clinical detection of intraocular complications.

A secondary outcome was paracentral macular volume (PMV), measured by spectral domain OCT (Heidelberg Spectralis Flex). Linear regression / paired t tests were used to compare rates of decline.

Results : Participants had between 6 and 8 intravitreal injections over 12 - 18 months. No adverse reactions (uveitis, raised IOP or media opacity) have been detected. The mean baseline PMV was 1.28 mm^3 (right),1.27 mm^3 (left).

3 patients exhibited progressive retinal thinning in both eyes (p<0.05), whereas retinal volume was stable bilaterally in 5 patients. Only patients younger than 8yrs exhibited active degeneration. In these 3 'active' patients, the rate of PMV loss was slower in the treated vs. the untreated eye (p=0.000042, p=0.0011, p=0.00022). The mean volume loss in the same patients was 14.4% (right), 21.2% (left), p<0.05.

Conclusions : Treatment with intravitreal rhTPP1 appears to be safe. Rapid retinal thinning was seen in both eyes of 3 of our youngest patients, confirming that these patients are in the active degenerative phase of the disease. In these 3 patients, treatment with intravitreal rhTPP1 reduced the rate of retinal volume loss.Intravitreal rhTPP1 appears to be a safe and effective treatment for CLN-2 related retinopathy, however commencement of treatment early in the course of disease is required for efficacy.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.