Phenylketonuria (PKU)

The key challenge in phenylketonuria (PKU) therapeutic development lies in achieving sustained phenylalanine reduction while overcoming blood-brain barrier penetration limitations. Protheragen leverages cutting-edge insights into the pathogenesis and genetic drivers of PKU to pioneer targeted therapies and precision animal models, accelerating preclinical drug development. Our goal is to offer reliable and end-to-end support to streamline your therapeutic development journey.

Introduction to Phenylketonuria (PKU)

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) activity, resulting in toxic accumulation of phenylalanine (Phe) and subsequent neurological damage. Characterized by hyperphenylalaninemia, untreated PKU leads to severe intellectual disability, seizures, and behavioral abnormalities. PKU affects 1 in 10,000-15,000 live births.

Fig.1 Pathological mechanisms involved in phenylketonuria (PKU) and other conditions with hyperphenylalaninemia (HPA). (Wyse A T S, et al., 2021)

Pathogenesis of Phenylketonuria (PKU)

Phenylketonuria (PKU) results from mutations in the PAH gene encoding phenylalanine hydroxylase, causing impaired conversion of phenylalanine (Phe) to tyrosine. This metabolic block leads to toxic Phe accumulation (>1200 μmol/L in classic PKU), which disrupts cerebral neurotransmitter synthesis (dopamine/serotonin deficiency) and myelin formation through competitive inhibition of large neutral amino acid transporters. The resultant neurotoxicity manifests as irreversible intellectual disability if untreated, with severity directly correlating to residual PAH enzyme activity.

Fig.2 Phenylketonuria (PKU) pathophysiology. (Borges A C, et al., 2022)

Therapeutic Development for Phenylketonuria (PKU)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Recognizing the complexity of diagnosing and treating phenylketonuria (PKU), Protheragen is committed to building a team of experts to provide cutting-edge diagnostic and therapeutic development solutions. Our commitment lies in providing a variety of customized therapy development services to meet the diverse research needs of our customers. We also excel in generating precise disease models that are carefully engineered to replicate the unique features of phenylketonuria (PKU).

Therapeutic Development Services

By Molecule Types

• Small Molecule Drug Development
• Cell Therapy Development
• Gene Therapy Development

• Therapeutic Antibody Development
• Therapeutic Peptide Development
• Therapeutic Protein Development

By Mechanism of Action

• Neuroprotective Agent Development
• Glutamate Modulator Development
• Anti-neuroinflammatory Drug Development
• Antioxidant Development

• Mitochondria-targeted Drug Development
• Protein Misfolding Inhibitor Development
• Protein Aggregation Inhibitor Development
• Excitotoxicity Inhibitor Development

Disease Model Development Services

In Vitro Model Development

• Patient-Derived Cell Model
• Neuronal Cell Model
• Glial Cell Model
• Co-Culture Model
• Brain Organoid
• Spinal Cord Organoid

Microfluidic Model Development

• Neurovascular Unit Model
• Axon Degeneration Model
• Neuroinflammation Model
• Neuromuscular Junction Model
• Synaptic Plasticity Model
• Organoid-on-a-Chip Model

Animal Model Development

• PAH Knockout Model: This model features complete PAH gene deletion, resulting in severe hyperphenylalaninemia.
• PAH*R243Q Knock-in Model: This model carries the Asian-prevalent PAH c.835T>C (p.R243Q) point mutation, exhibiting partial PAH activity and BH4-responsive hyperphenylalaninemia.