Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease
Abstract 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 deficiencie...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2021-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202114712 |
| _version_ | 1826932707263774720 |
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| author | Paul Wuh‐Liang Hwu Karl Kiening Irina Anselm David R Compton Takeshi Nakajima Thomas Opladen Phillip L Pearl Agathe Roubertie Thomas Roujeau Shin‐ichi Muramatsu |
| author_facet | Paul Wuh‐Liang Hwu Karl Kiening Irina Anselm David R Compton Takeshi Nakajima Thomas Opladen Phillip L Pearl Agathe Roubertie Thomas Roujeau Shin‐ichi Muramatsu |
| author_sort | Paul Wuh‐Liang Hwu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T18:02:12Z |
| format | Article |
| id | doaj.art-fb674fddecf64782b2382b315e8a5d34 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-17T17:18:47Z |
| publishDate | 2021-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-fb674fddecf64782b2382b315e8a5d342024-12-15T12:11:16ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-08-011391510.15252/emmm.202114712Gene therapy in the putamen for curing AADC deficiency and Parkinson's diseasePaul Wuh‐Liang Hwu0Karl Kiening1Irina Anselm2David R Compton3Takeshi Nakajima4Thomas Opladen5Phillip L Pearl6Agathe Roubertie7Thomas Roujeau8Shin‐ichi Muramatsu9Department of Medical Genetics and Pediatrics, National Taiwan University HospitalDivision of Stereotactic Neurosurgery, Department of Neurosurgery, University of Heidelberg Medical CenterDepartment of Neurology, Boston Children’s Hospital, Harvard Medical SchoolPreclinical Development (Gene Therapy), PTC TherapeuticsDepartment of Neurosurgery, Jichi Medical UniversityDivision of Child Neurology and Metabolic Disorders, University Children’s HospitalEpilepsy and Clinical Neurophysiology, William G. Lennox Chair and Professor of Neurology, Harvard Medical School, Boston Children’s HospitalPediatric Neurology Department, INM, INSERM, CHU Montpellier, University of MontpellierDepartment of Neurosurgery, Gui‐de‐Chauliac Hospital, Montpellier University HospitalDivision of Neurological Gene Therapy, Jichi Medical University, ShimotsukeAbstract 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.https://doi.org/10.15252/emmm.202114712AADC deficiencyaromatic l‐amino acid decarboxylasedopaminegene therapyputamen |
| spellingShingle | Paul Wuh‐Liang Hwu Karl Kiening Irina Anselm David R Compton Takeshi Nakajima Thomas Opladen Phillip L Pearl Agathe Roubertie Thomas Roujeau Shin‐ichi Muramatsu Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease EMBO Molecular Medicine AADC deficiency aromatic l‐amino acid decarboxylase dopamine gene therapy putamen |
| title | Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease |
| title_full | Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease |
| title_fullStr | Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease |
| title_full_unstemmed | Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease |
| title_short | Gene therapy in the putamen for curing AADC deficiency and Parkinson's disease |
| title_sort | gene therapy in the putamen for curing aadc deficiency and parkinson s disease |
| topic | AADC deficiency aromatic l‐amino acid decarboxylase dopamine gene therapy putamen |
| url | https://doi.org/10.15252/emmm.202114712 |
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