Intravitreal enzyme replacement therapy appears safe and effective for IRD

Findings from a recent review study suggests that intravitreal enzyme replacement therapy (IVT ERT) with a recombinant human tripeptidyl-peptidase1 (rhTPP1) may be a safe and effective treatment for neuronal ceroid lipofuscinosis type 2 (CLN2) retinopathy, an inherited retinal disease (IRD). The dosage, frequency, and ideal patient selection to achieve optimal outcomes requires further investigation, noted the researchers.

ERT is being explored in CLN2 related Batten disease, a fatal neurodegenerative condition associated with retinopathy and blindness that is caused by the deficiency of lysosomal enzyme TPP1. Previous studies have shown that cerliponase alfa, a rhTPP1 via intraventricular infusions, slows the rate of neurodegenerative decline but not retinopathy. A preclinical study of IVT rhTPP1 in a CLN2 canine model demonstrated efficacy in preserving retinal function and retinal morphology shown on histology. More recently, IVT administration of rhTPP1 was reported in a first-in-human compassionate use study. Patients received 12 to 18 months of 8-weekly IVT ERT (0.2 mg rhTPP-1 in 0.05 ml) in 1eye. Treatment modestly decreased the rate of retinal thinning. No significant ocular adverse reactions were observed.

Reference
Rodriguez-Martinez AC, Wawrzynski J, Henderson RH. Intravitreal enzyme replacement for inherited retinal diseases. Curr Opin Ophthalmol. Published December 27, 2023. doi: 10.1097/ICU.0000000000001029