Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones
Abstract Background Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial r...
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| Language: | English |
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BMC
2025-02-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03584-9 |
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| author | Wuh-Liang Hwu Hui-Min Lee John Devin Peipert Rongrong Zhang Christian Werner J. Rafael Sierra Thomas O’Connell Jonathan J. Woolley Marjorie Crowell Antonia Wang Ioannis Tomazos |
| author_facet | Wuh-Liang Hwu Hui-Min Lee John Devin Peipert Rongrong Zhang Christian Werner J. Rafael Sierra Thomas O’Connell Jonathan J. Woolley Marjorie Crowell Antonia Wang Ioannis Tomazos |
| author_sort | Wuh-Liang Hwu |
| collection | DOAJ |
| description | Abstract Background Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial results demonstrate continuous long-term improvement in motor development and cognitive function. We sought to characterize clinically meaningful change in motor function, as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score, and assess correlations with cognition and language domains of the Bayley-III and motor milestone (MM) achievement. Methods Data from N = 30 patients from three single-arm clinical studies of eladocagene exuparvovec were analyzed. Anchor-based estimation of the meaningful score difference (MSD) of Total PDMS-2 score was conducted using mean-difference and receiver operating characteristic curve (ROC) approaches. MM achievement served as the anchor defining meaningful change. Results An MSD of 40 points for Total PDMS-2 score was selected for analysis as it yielded specificity > 0.95 using the ROC approach, and generally aligned with the mean-difference approach. Cumulative incidence analysis reflected that 50% of patients treated with eladocagene exuparvovec may achieve the MSD of 40-point change in Total PDMS-2 score at 6 months, and 86% at 18 months. Correlations between measures were of large magnitude and improved over time (Month 6: r = 0.599 [p = 0.0032]; Month 18: r = 0.796 [p = 0.0002]; Month 60: r = 0.861 [p = 0.0007]). Conclusions The MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function. |
| format | Article |
| id | doaj-art-f15e91b84e8d4fc488727ee9237a3f40 |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-f15e91b84e8d4fc488727ee9237a3f402025-02-09T12:54:03ZengBMCOrphanet Journal of Rare Diseases1750-11722025-02-012011910.1186/s13023-025-03584-9Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestonesWuh-Liang Hwu0Hui-Min Lee1John Devin Peipert2Rongrong Zhang3Christian Werner4J. Rafael Sierra5Thomas O’Connell6Jonathan J. Woolley7Marjorie Crowell8Antonia Wang9Ioannis Tomazos10Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, National Taiwan University College of MedicineDepartment of Medical Genetics and Pediatrics, National Taiwan University Hospital, National Taiwan University College of MedicineCentre for Patient Reported Outcomes Research, Department of Applied Health Sciences, University of BirminghamPTC Therapeutics Sweden ABPTC Therapeutics Germany GmbHPTC TherapeuticsMedicus EconomicsMedicus EconomicsMedicus EconomicsPTC TherapeuticsPTC TherapeuticsAbstract Background Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial results demonstrate continuous long-term improvement in motor development and cognitive function. We sought to characterize clinically meaningful change in motor function, as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score, and assess correlations with cognition and language domains of the Bayley-III and motor milestone (MM) achievement. Methods Data from N = 30 patients from three single-arm clinical studies of eladocagene exuparvovec were analyzed. Anchor-based estimation of the meaningful score difference (MSD) of Total PDMS-2 score was conducted using mean-difference and receiver operating characteristic curve (ROC) approaches. MM achievement served as the anchor defining meaningful change. Results An MSD of 40 points for Total PDMS-2 score was selected for analysis as it yielded specificity > 0.95 using the ROC approach, and generally aligned with the mean-difference approach. Cumulative incidence analysis reflected that 50% of patients treated with eladocagene exuparvovec may achieve the MSD of 40-point change in Total PDMS-2 score at 6 months, and 86% at 18 months. Correlations between measures were of large magnitude and improved over time (Month 6: r = 0.599 [p = 0.0032]; Month 18: r = 0.796 [p = 0.0002]; Month 60: r = 0.861 [p = 0.0007]). Conclusions The MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function.https://doi.org/10.1186/s13023-025-03584-9Aromatic L-amino acid decarboxylase deficiencyMotor functionCognitive functionGene therapy |
| spellingShingle | Wuh-Liang Hwu Hui-Min Lee John Devin Peipert Rongrong Zhang Christian Werner J. Rafael Sierra Thomas O’Connell Jonathan J. Woolley Marjorie Crowell Antonia Wang Ioannis Tomazos Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones Orphanet Journal of Rare Diseases Aromatic L-amino acid decarboxylase deficiency Motor function Cognitive function Gene therapy |
| title | Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones |
| title_full | Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones |
| title_fullStr | Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones |
| title_full_unstemmed | Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones |
| title_short | Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones |
| title_sort | clinically meaningful improvements after gene therapy for aromatic l amino acid decarboxylase deficiency aadcd in the peabody developmental motor scale second edition pdms 2 and correlation with bayley iii scores and motor milestones |
| topic | Aromatic L-amino acid decarboxylase deficiency Motor function Cognitive function Gene therapy |
| url | https://doi.org/10.1186/s13023-025-03584-9 |
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