Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC

Mol Ther. 2006 Oct;14(4):564-70. doi: 10.1016/j.ymthe.2006.05.005. Epub 2006 Jul 7.


Dopamine, the major neurotransmitter depleted in Parkinson disease, can be synthesized and regulated in vivo with a combination of intrastriatal AAV-hAADC gene therapy and administration of the dopamine precursor l-Dopa. When tested in MPTP-lesioned monkeys, this approach resulted in long-term improvement in clinical rating scores, significantly lowered l-Dopa requirements, and a reduction in l-Dopa-induced side effects. Positron emission tomography with [(18)F]FMT confirmed persistent AADC activity, demonstrating for the first time that infusion of AAV vector into primate brain results in at least 6 years of transgene expression. AAV-hAADC restores the ability of the striatum to convert l-Dopa into dopamine efficiently. Introduction of this therapy into the clinic holds promise for Parkinson patients experiencing the motor complications that result from escalating l-Dopa requirements against a background of disease progression.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / genetics
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism*
  • Behavior, Animal
  • Dependovirus / genetics*
  • Gene Expression
  • Genetic Therapy*
  • Humans
  • Immunohistochemistry
  • Levodopa / pharmacology
  • Macaca mulatta
  • Male
  • Positron-Emission Tomography
  • Primate Diseases / chemically induced
  • Primate Diseases / genetics*
  • Primate Diseases / metabolism
  • Primate Diseases / therapy*
  • Time Factors


  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Aromatic-L-Amino-Acid Decarboxylases