Cerliponase alfa

Specifically, Cerliponase alfa is meant to slow loss of motor function in symptomatic children over three years old with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2).

[3] Approved by the United States Food and Drug Administration (FDA) on 27 April 2017, this is the first treatment for a neuronal ceroid lipofuscinosis of its kind, acting to slow disease progression rather than palliatively treat symptoms by giving patients the TPP1 enzyme they are lacking.

A band appeared to be missing at approximately 46 kDa, confirming its role in CLN2 disease, and almost the entire gene for this unknown protein was sequenced.

[9] In 2012, BioMarin began the first clinical trial on affected patients using their recombinant DNA technology cerliponase alfa which is synthesized using Chinese hamster ovarian (CHO) cell lines.

[4][15] Cerliponase alfa is the first FDA-approved treatment to slow loss of walking ability (ambulation) in symptomatic pediatric patients three years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency.

When the cerliponase alfa proenzyme reaches target neurons during administration, it binds mannose-6-phosphate receptors on the cell surface to trigger vesicle formation around the receptor-proenzyme complex.

[17][19] Like natural TPP1, cerliponase alfa functions as a serine protease, cleaving N-terminal tripeptides from a broad range of protein substrates.

In CLN2 disease, TPP1 is deficient or not made at all, meaning that proteins are unable to be degraded in the lysosome and accumulate, leading to damage in nerves.

[16] Therefore, cerliponase alfa is administered repeatedly to maintain sufficient levels of the recombinant TPP1 enzyme in place of the deficient form to degrade proteins and prevent further build up.