Drug Repurposing: The End of Medicines As We Knew Them

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.

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