Therapeutic Use of Phenylalanine Ammonia Lyase (PAL)
Phenylalanine hydroxylase (PAH) regulates the intermediary metabolism of phenylalanine (Phe) by converting Phe to tyrosine (Tyr). PAH deficiency causes hyperphenylalaninemia (HPA) and phenylketonuria (PKU), and in particular, high levels of phenylalanine can lead to brain dysfunction. Therefore, enzyme replacement therapy may be effective for patients with PKU.
Pegvaliase (Palynziq) is an enzyme that metabolizes phenylalanine (Phe), replacing the decreased PAH enzyme activity. Pegvaliase consists of recombinant phenylalanine ammonia lyase (PAL) that is linked to methoxypolyethyleneglycol (PEG), which prolongs its half-life in vivo. The mechanism of Pegvaliase is that Phe-metabolized enzyme PAL catalyzes the transformation of Phe into trans-quinic acid and ammonia, which are metabolized by the liver and then excreted in the urine. Being a homotetrameric protein with a molecular weight of 62 kD per monomer, recombinant PAL is produced in engineered bacteria Escherichia coli (E. coli) with a plasmid carrying the PAL gene from Anabaena variabilis. And Pegvaliase (Palynziq) is developed by BioMarin Pharmaceuticals.
Yaohai Bio-Pharma Offers One-Stop CDMO Solution for PAL
PAL Pipeline
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Generic Name
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Brand Name/ Altermative Name
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Expression System
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Indications
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Manufacturer
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R&D Stage
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Pegvaliase-PQPZ
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rAvPAL-PEG, Phenylase, PEG-PAL, BMN-165, Palynziq, パリンジック
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E. coli
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Phenylketonuria (PKU)
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BioMarin
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Approval
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CDX-6114
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Phenylketonuria therapeutic enzyme, CDX 6114
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Pending Update
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Phenylketonuria (PKU)
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Codexis,Nestlé
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Phase I
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Phenylalanine ammonia lyase encapsulated erythrocytes
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EryPAL, Erythrocyte encapsulated PAL EryDel, EryDel
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Pending Update
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Phenylketonuria (PKU)
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EryDel
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Pre-clinical
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PJ008
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Pending Update
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Pending Update
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Phenylketonuria (PKU)
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Chongqing Paijin Biotechnology Co., Ltd.
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Pre-clinical
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Labafenogene marselecobac
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SYN PKU, SYNB 1618, Labafenogene marselecobac
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Pending Update
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Phenylketonuria (PKU)
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Synlogic
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Phase II
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Domofenogene zalfaparvove
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BMN307
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Pending Update
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Phenylketonuria (PKU)
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BioMarin Pharmaceutical, Inc.
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Phase II
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mRNA-3283
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PAL mRNA
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Pending Update
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Phenylketonuria (PKU)
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Moderna, Inc.
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Pre-clinical
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Gene Therapy
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Pending Update
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Pending Update
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Phenylketonuria (PKU)
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Genzyme Corp.
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Pre-clinical
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