Dose selection for intracerebroventricular cerliponase alfa in children with CLN2 disease, translation from animal to human in a rare genetic disease.

ABSTRACT: Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an ultra-rare pediatric neurodegenerative disorder characterized by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). In the absence of adequate TPP1, lysosomal storage material accumulation occurs in the central nervous system (CNS) accompanied by neurodegeneration and neurological decline that culminates in childhood death. Cerliponase alfa is a recombinant human TPP1 enzyme replacement therapy administered via intracerebroventricular infusion and approved for the treatment of CLN2 disease. Here, we describe two allometric methods, calculated by scaling brain mass across species, that informed the human dose selection and exposure prediction of cerliponase alfa from preclinical studies in monkeys and a dog model of

SUBMITTER: Hammon K 

PROVIDER: S-EPMC8504808 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature