Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses.
Parkinson's disease (PD) is an increasingly prevalent neurologic condition for which symptomatic, but not preventative, treatment is available. Drug repurposing is an innovate drug discovery method that uncovers existing therapeutics to treat or prevent conditions for which they are not current...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0323761 |
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| author | Maria P Gorenflo Zhenxiang Gao Pamela B Davis David Kaelber Rong Xu |
| author_facet | Maria P Gorenflo Zhenxiang Gao Pamela B Davis David Kaelber Rong Xu |
| author_sort | Maria P Gorenflo |
| collection | DOAJ |
| description | Parkinson's disease (PD) is an increasingly prevalent neurologic condition for which symptomatic, but not preventative, treatment is available. Drug repurposing is an innovate drug discovery method that uncovers existing therapeutics to treat or prevent conditions for which they are not currently indicated, a method that could be applied to incurable diseases such as PD. A knowledge graph artificial intelligence prediction system was used to select potential drugs that could be used to treat or prevent PD, and amphetamine was identified as the strongest candidate. Retrospective cohort analysis on a large, electronic health record database of deidentified patients with attention deficit hyperactive disorder (the main diagnosis for which amphetamine is prescribed) revealed a significantly reduced hazard of developing PD in patients prescribed amphetamine versus patients not prescribed amphetamine at 2, 4, and 6 years: Hazard Ratio (95% Confidence Interval) = 0.59 (0.36, 0.98), 0.63 (0.42, 0.93), and 0.55 (0.38, 0.79). Pathway enrichment analysis confirmed that amphetamine targets many of the biochemical processes implicated in PD, such as dopaminergic synapses and neurodegeneration. Together, these observational findings suggest that therapeutic and legal amphetamine use may reduce the risk of developing PD, in contrast to previous work that found the inverse relationship in patients using amphetamine recreationally. |
| format | Article |
| id | doaj-art-4d99a430c5f54570a577882eb55e23b6 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4d99a430c5f54570a577882eb55e23b62025-08-20T02:26:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01205e032376110.1371/journal.pone.0323761Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses.Maria P GorenfloZhenxiang GaoPamela B DavisDavid KaelberRong XuParkinson's disease (PD) is an increasingly prevalent neurologic condition for which symptomatic, but not preventative, treatment is available. Drug repurposing is an innovate drug discovery method that uncovers existing therapeutics to treat or prevent conditions for which they are not currently indicated, a method that could be applied to incurable diseases such as PD. A knowledge graph artificial intelligence prediction system was used to select potential drugs that could be used to treat or prevent PD, and amphetamine was identified as the strongest candidate. Retrospective cohort analysis on a large, electronic health record database of deidentified patients with attention deficit hyperactive disorder (the main diagnosis for which amphetamine is prescribed) revealed a significantly reduced hazard of developing PD in patients prescribed amphetamine versus patients not prescribed amphetamine at 2, 4, and 6 years: Hazard Ratio (95% Confidence Interval) = 0.59 (0.36, 0.98), 0.63 (0.42, 0.93), and 0.55 (0.38, 0.79). Pathway enrichment analysis confirmed that amphetamine targets many of the biochemical processes implicated in PD, such as dopaminergic synapses and neurodegeneration. Together, these observational findings suggest that therapeutic and legal amphetamine use may reduce the risk of developing PD, in contrast to previous work that found the inverse relationship in patients using amphetamine recreationally.https://doi.org/10.1371/journal.pone.0323761 |
| spellingShingle | Maria P Gorenflo Zhenxiang Gao Pamela B Davis David Kaelber Rong Xu Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses. PLoS ONE |
| title | Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses. |
| title_full | Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses. |
| title_fullStr | Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses. |
| title_full_unstemmed | Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses. |
| title_short | Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses. |
| title_sort | amphetamine use and parkinson s disease integration of artificial intelligence prediction clinical corroboration and mechanism of action analyses |
| url | https://doi.org/10.1371/journal.pone.0323761 |
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