Open AccessGene therapy in the putamen for curing AADC deficiency and Parkinson's disease
Author(s) -
Hwu Paul WuhLiang,
Kiening Karl,
Anselm Irina,
Compton David R,
Nakajima Takeshi,
Opladen Thomas,
Pearl Phillip L,
Roubertie Agathe,
Roujeau Thomas,
Muramatsu Shinichi
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202114712
Subject(s) - putamen , dopamine , parkinson's disease , genetic enhancement , dopaminergic , medicine , neuroscience , disease , biology , gene , genetics
This commentary provides an overview of the putamen as an established target site for gene therapy in treating aromatic l ‐amino acid decarboxylase (AADC) deficiency and Parkinson’s disease, two debilitating neurological disorders that involve motor dysfunction caused by dopamine deficiencies. The neuroanatomy and the function of the putamen in motor control provide good rationales for targeting this brain structure. Additionally, the efficacy and safety of intraputaminal gene therapy demonstrate that restoration of dopamine synthesis in the putamen by using low doses of adeno‐associated viral vector serotype 2 to deliver the hAADC gene is well tolerated. This restoration leads to sustained improvements in motor and nonmotor symptoms of AADC deficiency and improved uptake and conversion of exogenous l ‐DOPA into dopamine in Parkinson’s patients.