Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy
2020-03-30Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy
Ther Clin Risk Manag. 2020; 16: 213–222. Published online 2020 Mar 30. doi: 10.2147/TCRM.S241048
PMID: 32280231
Nicola Specchio, Nicola Pietrafusa, Marina Trivisano
Summary: The natural history of CLN2 disease, its diagnosis and management, and the preclinical and clinical development of cerliponase alfa, were all described in this study. Cerliponase alfa administration in patients with CLN2 disease resulted in significant reductions in the rate of decline of motor and language functions.
Abstract
Background: Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a progressive neurodegenerative disease that results in early-onset, severe, progressive, neurological disabilities, leading to death in late childhood or early adolescence. Management has relied on symptomatic care, and supportive and palliative strategies, but the approval of the enzyme replacement therapy cerliponase alfa in the USA and Europe in 2017 brought different treatment opportunities. The natural history of CLN2 disease, its diagnosis and management, and the preclinical and clinical development of cerliponase alfa, were all described in this study.
Methods: A PubMed search for cerliponase alfa and rhTPP1 was conducted to identify preclinical and clinical studies.
Results: The hallmark-presenting symptoms of CLN2 disease are unprovoked seizures and a history of language delay, and progression involves motor dysfunction, and cognitive and visual decline. When administered intracerebroventricularly, cerliponase alfa demonstrated efficacy and tolerability in mouse and canine models of CLN2 disease.
Conclusion: Cerliponase alfa administration in patients with CLN2 disease resulted in significant reductions in the rate of decline of motor and language functions when compared to a natural history population. The approval of cerliponase alfa has brought a new era for CLN2 disease, emphasizing the importance of understanding different patterns of disease progression and clinical needs in treated patients.