Cerliponase alfa

CLN2 disease is a neurodegenerative disease associated with a variety of mutations leading to reduced activity or inactivation of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1), which removes tripeptides from the N-terminus of peptides in the central nervous system (CNS). TPP1 has no known substrate specificity. Deficiency in TPP1 activity results in the accumulation of ceroid lipofuscin in the lysosomes normally metabolized by TPP1 in the CNS, leading to massive glial activation and neuronal loss and a progressive decline in motor and cognitive function. Because TPP1 expression is developmentally controlled and peaks around the age of two to four, which is the onset of signs and symptoms of the classic late-infantile phenotype of CLN2 disease.

Cerliponase alfa (rhTTP1), a proenzyme, is taken up by target cells in the CNS and is translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor). Cerliponase alfa is activated in the lysosome and the activated proteolytic form of rhTPP1 cleaves tripeptides from the N-terminus of proteins.