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| Primary information |
|---|
| ID | 15122 |
| Therapeutic ID | Th1568 |
| Protein Name | Cerliponase alfa |
| Sequence | >Th1568_Cerliponase_alfa
SYSPEPDQRRTLPPGWVSLGRADPEEELSLTFALRQQNVERLSELVQAVSDPSSPQYGKYLTLENVADLVRPSPLTLHTVQKWLLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGAEFHHYVGGPTETHVVRSPHPYQLPQALAPHVDFVGGLHRFPPTSSLRQRPEPQVTGTVGLHLGVTPSVIRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDSDLAQFMRLFGGNFAHQASVARVVGQQGRGRAGIEASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQWLMLLSNESALPHVHTVSYGDDEDSLSSAYIQRVNTELMKAAARGLTLLFASGDSGAGCWSVSGRHQFRPTFPASSPYVTTVGGTSFQEPFLITNEIVDYISGGGFSNVFPRPSYQEEAVTKFLSSSPHLPPSSYFNASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSASTPVFGGILSLINEHRILSGRPPLGFLNPRLYQQHGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP
|
| Molecular Weight | 59 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Refer to FDA Label |
| Description | Cerliponase alfa is an enzyme replacement treatment for a specific form of Batten disease. It was the first FDA-approved treatment to slow loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. Intraventricular administration of the drug allows significant uptake into the brain. Cerliponase alfa was approved in April, 2017 (as Brineura). |
| Indication/Disease | Cerliponase alfa is a treatment for late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease to decelerate the progressive motor function decline in patients 3 years of age and older. CLN2 disease is a form of Batten disease, a rare inherited neurodegenerative disorder and is associated with seizures, ataxia, rapid loss of language and motor functions, blindness, and early death [L755]. It is caused by the lack the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) and subsequent accumulation of lysosomal storage materials normally metabolized by this enzyme in the central nervous system. |
| Pharmacodynamics | Cerliponase alfa contains the active substance tripeptidyl peptidase-1 (rhTPP1), a recombinant human lysosomal exopeptidase which cleaves the N-terminal of tripeptides with a broad substrate specificity. Cerliponase alfa slows the progressive decline in motor function caused by abnormal motor signalling in the brain by restoring the normal levels and activity of TPP1. |
| Mechanism of Action | The mature form of enzyme contains 5 consensus N-glycosylation sites with high mannose, phosphorylated high mannose and complex glycosylation structures. It is taken up by LINCL fibroblasts and 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 under low pH conditions and the activated proteolytic form of rhTPP1 cleaves tripeptides from the N-terminus of stored proteins. |
| Toxicity | No data from carcinogenicity, genotoxicity, and fertility studies. Unwanted effects of cerliponase alfa treatment include pyrexia, ECG abnormalities, decreased CSF protein, seizure and hypersensitivity. |
| Metabolism | Predicted to be metabolized through peptide hydrolysis. |
| Absorption | Refer to FDA Label |
| The estimated CSF volume of distribution of cerliponase alfa following intraventricular infusion of 300mg of Brineura (median Vss = 245 mL) exceeds the typical CSF volume (100 mL) [FDA label]. |
| Clearance | Refer to FDA Label |
| Categories | Alimentary Tract and Metabolism |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Cation-independent mannose-6-phosphate receptor |
| Brand Name | Brineura |
| Company | BioMarin Pharmaceutical Inc. |
| Brand Description | BioMarin Pharmaceutical Inc. |
| Prescribed For | Intraventricular |
| Chemical Name | 150 mg/5mL |
| Formulation | Brineura is contraindicated in patients with:any sign or symptom of acute, unresolved localized infection on or around the device insertion site (e.g. cellulitis or abscess); or suspected or confirmed CNS infection (e.g. cloudy CSF or positive CSF gram stain, or meningitis) [see WARNINGS AND PRECAUTIONS].any acute intraventricular access device-related complication (e.g., leakage, extravasation of fluid, or device failure) [see WARNINGS AND PRECAUTIONS].ventriculoperitoneal shunts. |
| Physical Appearance | fever, ECG abnormalities, increased or decreased cerebrospinal fluid (CSF) protein, vomiting, seizures, hypersensitivity, blood clotting, headache, irritability, increased white blood cell count (pleocytosis), device-related infection, slow heart rate, feeling jittery, and low blood pressure (hypotension). |
| Route of Administration | Brineura is used to slow the loss of ability to crawl or walk in children with symptoms of a rare genetic condition called ceroid lipofuscinosis type 2 disease (CLN2). Brineura is for use in children who are at least 3 years old. Brineura may help slow the loss of certain physical abilities in children... |
| Recommended Dosage | Brineura (cerliponase alfa) injection is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase1 (TPP1) deficiency. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |