Phenylalanine Ammonia Lyase (PAL)

Modality

Phenylalanine Ammonia Lyase (PAL)

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

Generic Name	Brand Name/ Altermative Name	Expression System	Indications	Manufacturer	R&D Stage
Pegvaliase-PQPZ	rAvPAL-PEG, Phenylase, PEG-PAL, BMN-165, Palynziq, パリンジック	E. coli	Phenylketonuria (PKU)	BioMarin	Approval
CDX-6114	Phenylketonuria therapeutic enzyme, CDX 6114	Pending Update	Phenylketonuria (PKU)	Codexis,Nestlé	Phase I
Phenylalanine ammonia lyase encapsulated erythrocytes	EryPAL, Erythrocyte encapsulated PAL EryDel, EryDel	Pending Update	Phenylketonuria (PKU)	EryDel	Pre-clinical
PJ008	Pending Update	Pending Update	Phenylketonuria (PKU)	Chongqing Paijin Biotechnology Co., Ltd.	Pre-clinical
Labafenogene marselecobac	SYN PKU, SYNB 1618, Labafenogene marselecobac	Pending Update	Phenylketonuria (PKU)	Synlogic	Phase II
Domofenogene zalfaparvove	BMN307	Pending Update	Phenylketonuria (PKU)	BioMarin Pharmaceutical, Inc.	Phase II
mRNA-3283	PAL mRNA	Pending Update	Phenylketonuria (PKU)	Moderna, Inc.	Pre-clinical
Gene Therapy	Pending Update	Pending Update	Phenylketonuria (PKU)	Genzyme Corp.	Pre-clinical

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Phenylalanine Ammonia Lyase (PAL)

Modality