A new perspective on the treatment of aromatic L-amino acid decarboxylase deficiency

Mol Genet Metab. 2009 May;97(1):6-14. doi: 10.1016/j.ymgme.2009.01.010. Epub 2009 Jan 27.

Abstract

The final step in production of the neurotransmitters dopamine and serotonin is catalyzed by aromatic l-amino acid decarboxylase (AADC). AADC deficiency is a debilitating genetic condition that results in a deficit in these neurotransmitters, and manifests in infancy as a severe movement disorder with developmental delay. Response to current treatments is often disappointing. We have reviewed the literature to look for improvements to the current treatment strategy and also for new directions for AADC deficiency treatment. There may be differences in the mode of action, side-effect risk and effectiveness between different dopamine agonists and monoamine oxidase inhibitors currently used for AADC deficiency treatment. The range of these drugs used requires re-evaluation as some may have greater efficacy than others. Pyridoxal 5'-phosphate, the AADC cofactor may stabilize AADC and could increase AADC activity. Pyridoxal 5'-phosphate could have advantages as a treatment instead of pyridoxine. Atypical neuroleptics and peripheral AADC inhibitors both increase AADC activity in vivo and could be a future direction for AADC deficiency treatment and related conditions. Parkinson's disease gene therapy to deliver and express the human AADC gene in striatum is being tested in humans. Consequently gene therapy for AADC deficiency could be a realistic aim however an animal model of AADC deficiency is important for further progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / deficiency*
  • Humans
  • Metabolic Diseases / enzymology
  • Metabolic Diseases / genetics
  • Metabolic Diseases / therapy*

Substances

  • Aromatic-L-Amino-Acid Decarboxylases