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Trends in enzyme therapy for phenylketonuria

Woomi Kim1, Heidi Erlandsen, Sankar Surendran

  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|August 6, 2004
PubMed

Insights

Phenylketonuria (PKU) treatment faces challenges with lifelong dietary adherence. Enzyme replacement therapy, particularly using modified phenylalanine hydroxylase (PAH), shows promise for better phenylalanine control in PKU patients.

Area of Science:

  • Biochemistry
  • Metabolic Disorders
  • Enzyme Therapy

Background:

  • Phenylketonuria (PKU) is a genetic disorder of amino acid metabolism due to phenylalanine hydroxylase (PAH) deficiency.
  • Lifelong dietary management of phenylalanine (Phe) is crucial but challenging for PKU patients.
  • Alternative therapies are needed due to the difficulties in maintaining strict dietary control.

Purpose of the Study:

  • To review advancements in enzyme replacement therapy (ERT) for PKU.
  • To discuss the development of stable and functional enzyme variants for PKU treatment.

Main Methods:

  • Review of scientific literature on PKU enzyme replacement strategies.
  • Discussion of two primary enzyme modalities: PAH and phenylalanine ammonia-lyase (PAL).
  • Focus on modifications to improve enzyme stability and function.

Main Results:

  • Developing effective and stable enzyme therapies for PKU has been challenging.
  • Polyethylene glycol (PEG)-modified forms of PAH have demonstrated improved stability and activity.
  • These modified enzymes represent a promising avenue for PKU treatment.

Conclusions:

  • Enzyme replacement therapy is an emerging strategy for PKU management.
  • Modified phenylalanine hydroxylase (PAH) shows significant potential for improving PKU treatment outcomes.
  • Further development of stable enzyme therapeutics could alleviate the burden of lifelong dietary restrictions in PKU.

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