Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework
A rich pipeline of therapeutic candidates is advancing for Parkinson’s disease, many of which are targeting the underlying pathophysiology of disease. Emerging evidence grounded in novel genetics and biomarker discoveries is illuminating the true promise of precision medicine-based therapeutic strat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Systems Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fsysb.2024.1351555/full |
| _version_ | 1797268735687393280 |
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| author | Christopher Denaro Diane Stephenson Martijn L. T. M. Müller Benedetto Piccoli Benedetto Piccoli Karim Azer |
| author_facet | Christopher Denaro Diane Stephenson Martijn L. T. M. Müller Benedetto Piccoli Benedetto Piccoli Karim Azer |
| author_sort | Christopher Denaro |
| collection | DOAJ |
| description | A rich pipeline of therapeutic candidates is advancing for Parkinson’s disease, many of which are targeting the underlying pathophysiology of disease. Emerging evidence grounded in novel genetics and biomarker discoveries is illuminating the true promise of precision medicine-based therapeutic strategies for PD. There has been a growing effort to investigate disease-modifying therapies by designing clinical trials for genetic forms of PD - providing a clearer link to underlying pathophysiology. Leading candidate genes based on human genetic findings that are under active investigation in an array of basic and translational models include SNCA, LRRK2, and GBA. Broad investigations across mechanistic models show that these genes signal through common molecular pathways, namely, autosomal lysosomal pathways, inflammation and mitochondrial function. Therapeutic clinical trials to date based on genetically defined targets have not yet achieved approvals; however, much is to be learned from such pioneering trials. Fundamental principles of drug development that include proof of pharmacology in target tissue are critical to have confidence in advancing such precision-based therapies. There is a clear need for downstream biomarkers of leading candidate therapies to demonstrate proof of mechanism. The current regulatory landscape is poised and primed to support translational modeling strategies for the effective advancement of PD disease-modifying therapeutic candidates. A convergence of rich complex data that is available, the regulatory framework of model informed drug development (MIDD), and the new biological integrated staging frameworks when combined are collectively setting the stage for advancing new approaches in PD to accelerate progress. This perspective review highlights the potential of quantitative systems pharmacology (QSP) modeling in contributing to the field and hastening the pace of progress in advancing collaborative approaches for urgently needed PD disease-modifying treatments. |
| first_indexed | 2024-04-25T01:37:12Z |
| format | Article |
| id | doaj.art-f28f045c4f2845ea9ef9c8eca3076802 |
| institution | Directory Open Access Journal |
| issn | 2674-0702 |
| language | English |
| last_indexed | 2024-04-25T01:37:12Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Biology |
| spelling | doaj.art-f28f045c4f2845ea9ef9c8eca30768022024-03-08T09:24:16ZengFrontiers Media S.A.Frontiers in Systems Biology2674-07022024-03-01410.3389/fsysb.2024.13515551351555Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and frameworkChristopher Denaro0Diane Stephenson1Martijn L. T. M. Müller2Benedetto Piccoli3Benedetto Piccoli4Karim Azer5Center for Computational and Integrative Biology, Rutgers University, Camden, NJ, United StatesCritical Path Institute, Tucson, AZ, United StatesCritical Path Institute, Tucson, AZ, United StatesCenter for Computational and Integrative Biology, Rutgers University, Camden, NJ, United StatesDepartment of Mathematical Sciences, Rutgers University—Camden, Camden, NJ, United StatesAxcella, Cambridge, MA, United StatesA rich pipeline of therapeutic candidates is advancing for Parkinson’s disease, many of which are targeting the underlying pathophysiology of disease. Emerging evidence grounded in novel genetics and biomarker discoveries is illuminating the true promise of precision medicine-based therapeutic strategies for PD. There has been a growing effort to investigate disease-modifying therapies by designing clinical trials for genetic forms of PD - providing a clearer link to underlying pathophysiology. Leading candidate genes based on human genetic findings that are under active investigation in an array of basic and translational models include SNCA, LRRK2, and GBA. Broad investigations across mechanistic models show that these genes signal through common molecular pathways, namely, autosomal lysosomal pathways, inflammation and mitochondrial function. Therapeutic clinical trials to date based on genetically defined targets have not yet achieved approvals; however, much is to be learned from such pioneering trials. Fundamental principles of drug development that include proof of pharmacology in target tissue are critical to have confidence in advancing such precision-based therapies. There is a clear need for downstream biomarkers of leading candidate therapies to demonstrate proof of mechanism. The current regulatory landscape is poised and primed to support translational modeling strategies for the effective advancement of PD disease-modifying therapeutic candidates. A convergence of rich complex data that is available, the regulatory framework of model informed drug development (MIDD), and the new biological integrated staging frameworks when combined are collectively setting the stage for advancing new approaches in PD to accelerate progress. This perspective review highlights the potential of quantitative systems pharmacology (QSP) modeling in contributing to the field and hastening the pace of progress in advancing collaborative approaches for urgently needed PD disease-modifying treatments.https://www.frontiersin.org/articles/10.3389/fsysb.2024.1351555/fullquantitative systems pharmacologyprecision medicinetranslational researchdisease modifying therapygeneticsbiomarkers |
| spellingShingle | Christopher Denaro Diane Stephenson Martijn L. T. M. Müller Benedetto Piccoli Benedetto Piccoli Karim Azer Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework Frontiers in Systems Biology quantitative systems pharmacology precision medicine translational research disease modifying therapy genetics biomarkers |
| title | Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework |
| title_full | Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework |
| title_fullStr | Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework |
| title_full_unstemmed | Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework |
| title_short | Advancing precision medicine therapeutics for Parkinson’s utilizing a shared quantitative systems pharmacology model and framework |
| title_sort | advancing precision medicine therapeutics for parkinson s utilizing a shared quantitative systems pharmacology model and framework |
| topic | quantitative systems pharmacology precision medicine translational research disease modifying therapy genetics biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fsysb.2024.1351555/full |
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