First in man study of intravitreal tripeptidyl peptidase 1 for CLN2 retinopathy.

Autor: Wawrzynski J; UCL Great Ormond Street Institute of Child Health, London, UK.; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Martinez AR; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Thompson DA; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Ram D; Manchester University NHS Foundation Trust, Manchester, UK., Bowman R; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Whiteley R; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Gan C; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Harding L; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Mortensen A; Batten Disease Family Association, Shipley, UK., Mills P; UCL Great Ormond Street Institute of Child Health, London, UK.; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Gissen P; UCL Great Ormond Street Institute of Child Health, London, UK.; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK., Henderson RH; UCL Great Ormond Street Institute of Child Health, London, UK. Robert.Henderson@gosh.nhs.uk.; NIHR Biomedical Research Centre, Great Ormond Street Hospital, London, UK. Robert.Henderson@gosh.nhs.uk.
Jazyk: angličtina
Zdroj: Eye (London, England) [Eye (Lond)] 2024 Apr; Vol. 38 (6), pp. 1176-1182. Date of Electronic Publication: 2023 Dec 04.
DOI: 10.1038/s41433-023-02859-4
Abstrakt: Background/objectives: CLN2 Batten Disease is a fatal neurodegenerative condition of childhood associated with retinal dystrophy and blindness. Intracerebroventricular infusion of rhTPP1 greatly slows the rate of neurodegenerative decline but not retinopathy. Intravitreal rhTPP1 is known to slow retinal degeneration in a canine model of CLN2. We report a first-in-man controlled clinical trial of intravitreal rhTPP1 for CLN2 associated retinal dystrophy.
Subjects/methods: 8 children aged 5-9 with CLN2 Batten Disease were prospectively enroled. Severely affected patients were preferentially selected, provided that vision was better than no perception of light. Children underwent 8 weekly intravitreal injections of rhTPP1 (0.2 mg in 0.05 ml) into the right eye for 12-18 months. The left eye was untreated and acts as a paired control. The primary outcome was safety based on the clinical detection of complications. A secondary outcome was paracentral macular volume (PMV) measured by spectral domain OCT. Linear regression/paired t tests were used to compare rates of decline.
Results: No severe adverse reactions (uveitis, raised IOP, media opacity) occurred. The mean baseline PMV was 1.28 mm 3 (right), 1.27 mm 3 (left). 3 of the youngest patients exhibited bilateral progressive retinal thinning (p < 0.05), whereas retinal volume was stable in the remaining 5 patients. In the 3 patients undergoing retinal degeneration, the rate of PMV loss was slower in the treated vs. untreated eye (p = 0.000042, p = 0.0011, p = 0.00022).
Conclusions: Intravitreal rhTPP1 appears to be a safe and effective treatment for CLN2 related retinopathy however commencement of treatment early in the course of disease is more likely to be efficacious.
(© 2023. The Author(s).)
Databáze: MEDLINE
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