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      Drug Repurposing: The End of Medicines As We Knew Them

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      conference-abstract
        1 ,
      RExPO23 Conference
      REPO4EU
      RExPO23
      25-26 October 2023
      Drug Repurposing, Target Discovery, Phase II trials, Phase III trials, Regulatory Science, Disease modules, Signaling modules, Network Pharmacology, Pathways, Driver Genes
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            Abstract

            For decades classical drug discovery has been an efficacy crisis [1]. Drug repurposing has substantial potential, simply because it is faster and cheaper to reach patient benefit. So far, however, drug repurposing has been serendipitous and thus bears the risk of being equally risky, just failing faster and cheaper. The reason for both is the fact that we hardly understand any disease. That’s why we name diseases only by a symptom in an organ and therapeutically can only alleviate symptoms. For drug discovery, this has led to a “Better-than-the-Beatles” problem: If the standard of care drug is symptom-based, it’s hard to outperform this drug with just another symptom-based drug. For the patients, the biggest drawback is that symptom-based therapy will not cure and instead makes many diseases require chronic therapy. Patients become chronically ill. There are many reasons for this innovation roadblock. The biggest conceptual error in Medicine, however, was to split up the human body organ by organ, including organ-specific clinics, specialists, and research disciplines. We believe that we can define a disease by looking at one organ; any symptom in a different organ must be a different disease. Really? Rare diseases tell us, no! A big data-driven, holistic approach integrates all medical knowledge back into Systems Medicine to overcome this silo thinking by data science and bioinformatics. It revolutionizes how we define diseases. Descriptive disease phenotypes are replaced by mechanistic definitions based on small cellular signaling modules that have become dysfunctional [2]. Upon diagnosis of these dysfunctional signaling modules in a patient, precise and effective therapeutic intervention is achieved by targeting several points in these networks at low doses, with fewer side effects and high efficacy. For this network pharmacology approach [3, 4], we hardly need new compounds. In most if not all cases, we can repurpose already registered drugs, e.g., in peripheral artery disease (CIPER), ischemic stroke (REPO-STROKE IIa), and heart failure with preserved ejection fraction (REPO-HFPEF II), and more, obviating the need and costs for classical drug discovery, and speeding up the clinical translation and patent benefit. Thus, how we discover new medicine will radically change, from chronic treatment to cure, from new drugs (with unknown risks) to old drugs (with known risks), and ideally prevention.

            Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov. 2012 Mar 1;11(3):191-200. doi: 10.1038/nrd3681. PMID: 22378269.

            Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, Schmidt HHHW. Network pharmacology: curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci. 2022 Feb;43(2):136-150. doi: 10.1016/j.tips.2021.11.004. Epub 2021 Dec 9. PMID: 34895945..

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            Langhauser F, Casas AI, Dao VT, Guney E, Menche J, Geuss E, Kleikers PWM, López MG, Barabási AL, Kleinschnitz C, Schmidt HHHW. A diseasome cluster-based drug repurposing of soluble guanylate cyclase activators from smooth muscle relaxation to direct neuroprotection. NPJ Syst Biol Appl. 2018 Feb 5;4:8. doi: 10.1038/s41540-017-0039-7. PMID: 29423274; PMCID: PMC5799370.

            Content

            Author and article information

            Conference
            RExPO23 Conference
            REPO4EU
            13 October 2023
            Affiliations
            [1 ] Pharmacology and Personalised Medicine, Faculty of Health, Medicine and Life Science ( https://ror.org/02jz4aj89)
            Author notes
            Author information
            https://orcid.org/0000-0003-0419-5549
            Article
            10.58647/REXPO.23000030.v1
            928a8a9d-42f8-493e-9890-9ef93167e322

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

            RExPO23
            2
            Stockholm, Sweden
            25-26 October 2023
            History
            : 13 October 2023
            Funding
            Funded by: funder-id http://dx.doi.org/10.13039/100018693, HORIZON EUROPE Framework Programme;
            Funded by: funder-id http://dx.doi.org/10.13039/100010661, Horizon 2020 Framework Programme;
            Categories

            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Pharmacology & Pharmaceutical medicine
            Drug Repurposing,Target Discovery,Phase II trials,Phase III trials,Regulatory Science,Disease modules,Signaling modules,Network Pharmacology,Pathways,Driver Genes

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