Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics
Abstract The scarcity of effective biomarkers and therapeutic strategies for predicting disease onset and progression in neurodegenerative diseases such as Alzheimer’s disease (AD) is a major challenge. Conventional drug discovery approaches have been unsuccessful in providing efficient intervention...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-92593-6 |
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| author | Carla Cuní-López Romal Stewart Satomi Okano Garry L. Redlich Mark W. Appleby Anthony R. White Hazel Quek |
| author_facet | Carla Cuní-López Romal Stewart Satomi Okano Garry L. Redlich Mark W. Appleby Anthony R. White Hazel Quek |
| author_sort | Carla Cuní-López |
| collection | DOAJ |
| description | Abstract The scarcity of effective biomarkers and therapeutic strategies for predicting disease onset and progression in neurodegenerative diseases such as Alzheimer’s disease (AD) is a major challenge. Conventional drug discovery approaches have been unsuccessful in providing efficient interventions due to their ‘one-size-fits-all’ nature. As an alternative, personalised drug development holds promise to pre-select responders and identifying suitable indicators of drug efficacy. In this exploratory study, we have established a pipeline with the potential to guide patient stratification studies before clinical trials. This pipeline uses 2D and 3D in vitro models of monocyte-derived microglia-like cells (MDMi) from AD and mild cognitive impairment (MCI) patients, and matched healthy control (HC) individuals. By profiling cytokine responses in these models using multidimensional analyses, we have observed that the 3D model offers a more defined separation of profiles between individuals based on disease status. While this pilot study focuses on AD and MCI, future investigations incorporating other neurodegenerative disorders will be necessary to validate the pipeline’s findings and demonstrate its broader applicability. |
| format | Article |
| id | doaj-art-8512c06f8e7b4d7184c6d22e7a592ea8 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8512c06f8e7b4d7184c6d22e7a592ea82025-08-20T03:01:38ZengNature PortfolioScientific Reports2045-23222025-03-0115111210.1038/s41598-025-92593-6Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeuticsCarla Cuní-López0Romal Stewart1Satomi Okano2Garry L. Redlich3Mark W. Appleby4Anthony R. White5Hazel Quek6Brain and Mental Health, QIMR Berghofer Medical Research InstituteBrain and Mental Health, QIMR Berghofer Medical Research InstituteStatistics, QIMR Berghofer Medical Research InstituteImplicit BioscienceImplicit BioscienceBrain and Mental Health, QIMR Berghofer Medical Research InstituteBrain and Mental Health, QIMR Berghofer Medical Research InstituteAbstract The scarcity of effective biomarkers and therapeutic strategies for predicting disease onset and progression in neurodegenerative diseases such as Alzheimer’s disease (AD) is a major challenge. Conventional drug discovery approaches have been unsuccessful in providing efficient interventions due to their ‘one-size-fits-all’ nature. As an alternative, personalised drug development holds promise to pre-select responders and identifying suitable indicators of drug efficacy. In this exploratory study, we have established a pipeline with the potential to guide patient stratification studies before clinical trials. This pipeline uses 2D and 3D in vitro models of monocyte-derived microglia-like cells (MDMi) from AD and mild cognitive impairment (MCI) patients, and matched healthy control (HC) individuals. By profiling cytokine responses in these models using multidimensional analyses, we have observed that the 3D model offers a more defined separation of profiles between individuals based on disease status. While this pilot study focuses on AD and MCI, future investigations incorporating other neurodegenerative disorders will be necessary to validate the pipeline’s findings and demonstrate its broader applicability.https://doi.org/10.1038/s41598-025-92593-6Preclinical drug testingPreclinical pipeline for predictionMonocyte-derived microgliaMDMi2D and 3D in vitro modelsPatient stratification |
| spellingShingle | Carla Cuní-López Romal Stewart Satomi Okano Garry L. Redlich Mark W. Appleby Anthony R. White Hazel Quek Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics Scientific Reports Preclinical drug testing Preclinical pipeline for prediction Monocyte-derived microglia MDMi 2D and 3D in vitro models Patient stratification |
| title | Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics |
| title_full | Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics |
| title_fullStr | Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics |
| title_full_unstemmed | Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics |
| title_short | Exploring a patient-specific in vitro pipeline for stratification and drug response prediction of microglia-based therapeutics |
| title_sort | exploring a patient specific in vitro pipeline for stratification and drug response prediction of microglia based therapeutics |
| topic | Preclinical drug testing Preclinical pipeline for prediction Monocyte-derived microglia MDMi 2D and 3D in vitro models Patient stratification |
| url | https://doi.org/10.1038/s41598-025-92593-6 |
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