Patient selection considerations for AADC deficiency gene therapy
Abstract Background Aromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare, severe neurological disorder caused by pathogenic variants in the dopa decarboxylase (DDC) gene, resulting in a combined deficiency of monoamine neurotransmitters. Clinically, patients present with a range of dysfun...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-03-01
|
| Series: | Annals of the Child Neurology Society |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cns3.20052 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850184783056863232 |
|---|---|
| author | Agathe Roubertie Irina Anselm Bruria Ben‐Zeev Wuh‐Liang Hwu Ashutosh Kumar Berrin Monteleone Shin‐ichi Muramatsu Vincenzo Leuzzi Salvador Ibáñez Scellig Stone Phillip L. Pearl |
| author_facet | Agathe Roubertie Irina Anselm Bruria Ben‐Zeev Wuh‐Liang Hwu Ashutosh Kumar Berrin Monteleone Shin‐ichi Muramatsu Vincenzo Leuzzi Salvador Ibáñez Scellig Stone Phillip L. Pearl |
| author_sort | Agathe Roubertie |
| collection | DOAJ |
| description | Abstract Background Aromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare, severe neurological disorder caused by pathogenic variants in the dopa decarboxylase (DDC) gene, resulting in a combined deficiency of monoamine neurotransmitters. Clinically, patients present with a range of dysfunctions that impact motor, autonomic, and cognitive development. The constellation of symptoms of AADC deficiency varies among patients, and clinical presentation falls across a wide spectrum. However, most patients with AADC deficiency experience significant impairments when compared with children with normal development, irrespective of genotype, phenotype, or disease severity. Further, AADC deficiency is associated with increased mortality. Methods In response to the recent approval of a disease‐modifying gene therapy for AADC deficiency, this review presents considerations for the selection of patients for treatment. Conclusion Suggested clinical criteria to determine whether a patient is a candidate for gene therapy are: (1) genetically and biochemically confirmed AADC deficiency; (2) lack of achievement of gross motor milestones and/or persistence of clinically significant movement disorders; (3) persistent neurocognitive or systemic symptoms secondary to AADC deficiency despite standard medical therapy; and (4) informed parental/guardian decision and consent to treatment. |
| format | Article |
| id | doaj-art-deca6b443a2e40fb99fb7e172d08a585 |
| institution | OA Journals |
| issn | 2831-3267 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of the Child Neurology Society |
| spelling | doaj-art-deca6b443a2e40fb99fb7e172d08a5852025-08-20T02:16:56ZengWileyAnnals of the Child Neurology Society2831-32672024-03-0121535910.1002/cns3.20052Patient selection considerations for AADC deficiency gene therapyAgathe Roubertie0Irina Anselm1Bruria Ben‐Zeev2Wuh‐Liang Hwu3Ashutosh Kumar4Berrin Monteleone5Shin‐ichi Muramatsu6Vincenzo Leuzzi7Salvador Ibáñez8Scellig Stone9Phillip L. Pearl10Départment de Neuropédiatrie Centre Hospitalier Universitaire de Montpellier Montpellier FranceDepartment of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USASackler Faculty of Medicine Tel Aviv University Tel Aviv IsraelDepartment of Medical Genetics National Taiwan University Hospital Taipei City TaiwanDepartment of Pediatrics and Neurology Penn State Health Hershey Pennsylvania USADepartment of Clinical Genetics NYU Long Island School of Medicine New York New York USADivision of Neurological Gene Therapy, Center for Innovation Jichi Medical University Tochigi JapanDepartment of Human Neuroscience Sapienza University of Rome Rome ItalyDepartment of Pediatric Neurology Arrixaca University Hospital Murcia SpainDepartment of Neurosurgery, Boston Children's Hospital Harvard Medical School Boston Massachusetts USADepartment of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USAAbstract Background Aromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare, severe neurological disorder caused by pathogenic variants in the dopa decarboxylase (DDC) gene, resulting in a combined deficiency of monoamine neurotransmitters. Clinically, patients present with a range of dysfunctions that impact motor, autonomic, and cognitive development. The constellation of symptoms of AADC deficiency varies among patients, and clinical presentation falls across a wide spectrum. However, most patients with AADC deficiency experience significant impairments when compared with children with normal development, irrespective of genotype, phenotype, or disease severity. Further, AADC deficiency is associated with increased mortality. Methods In response to the recent approval of a disease‐modifying gene therapy for AADC deficiency, this review presents considerations for the selection of patients for treatment. Conclusion Suggested clinical criteria to determine whether a patient is a candidate for gene therapy are: (1) genetically and biochemically confirmed AADC deficiency; (2) lack of achievement of gross motor milestones and/or persistence of clinically significant movement disorders; (3) persistent neurocognitive or systemic symptoms secondary to AADC deficiency despite standard medical therapy; and (4) informed parental/guardian decision and consent to treatment.https://doi.org/10.1002/cns3.20052AADC deficiencygene therapyrare disease |
| spellingShingle | Agathe Roubertie Irina Anselm Bruria Ben‐Zeev Wuh‐Liang Hwu Ashutosh Kumar Berrin Monteleone Shin‐ichi Muramatsu Vincenzo Leuzzi Salvador Ibáñez Scellig Stone Phillip L. Pearl Patient selection considerations for AADC deficiency gene therapy Annals of the Child Neurology Society AADC deficiency gene therapy rare disease |
| title | Patient selection considerations for AADC deficiency gene therapy |
| title_full | Patient selection considerations for AADC deficiency gene therapy |
| title_fullStr | Patient selection considerations for AADC deficiency gene therapy |
| title_full_unstemmed | Patient selection considerations for AADC deficiency gene therapy |
| title_short | Patient selection considerations for AADC deficiency gene therapy |
| title_sort | patient selection considerations for aadc deficiency gene therapy |
| topic | AADC deficiency gene therapy rare disease |
| url | https://doi.org/10.1002/cns3.20052 |
| work_keys_str_mv | AT agatheroubertie patientselectionconsiderationsforaadcdeficiencygenetherapy AT irinaanselm patientselectionconsiderationsforaadcdeficiencygenetherapy AT bruriabenzeev patientselectionconsiderationsforaadcdeficiencygenetherapy AT wuhlianghwu patientselectionconsiderationsforaadcdeficiencygenetherapy AT ashutoshkumar patientselectionconsiderationsforaadcdeficiencygenetherapy AT berrinmonteleone patientselectionconsiderationsforaadcdeficiencygenetherapy AT shinichimuramatsu patientselectionconsiderationsforaadcdeficiencygenetherapy AT vincenzoleuzzi patientselectionconsiderationsforaadcdeficiencygenetherapy AT salvadoribanez patientselectionconsiderationsforaadcdeficiencygenetherapy AT scelligstone patientselectionconsiderationsforaadcdeficiencygenetherapy AT philliplpearl patientselectionconsiderationsforaadcdeficiencygenetherapy |