Zusammenfassung
Die verbesserte Therapie und Prophylaxe von Herz-Kreislauf-Erkrankungen hat wie kein anderer Bereich der Medizin zum Anstieg der Lebenserwartung beigetragen. Dennoch bleiben viele kardiologische Krankheiten schlecht therapierbar, und Standardtherapien nutzen nur einer Minderheit von Patienten oder verursachen mehr Nebenwirkungen als Nutzen. Personalisierte Ansätze versprechen neue Lösungswege. Die seltenen monogenen Herz-Kreislauf-Erkrankungen sind hierfür paradigmatisch und lassen sich heute in Einzelfällen „mutationsspezifisch“ behandeln. Dennoch sind die Erfolge insgesamt noch bescheiden. Das „next generation sequencing“ wird die Identifizierung krankheitsverursachender Mutationen erleichtern. Zellkulturmodelle auf der Basis induzierter pluripotenter Stammzellen lassen eine individuelle Testung pharmakologischer oder gentherapeutischer Therapieansätze erwarten. Gegenwärtig noch von untergeordneter klinischer Bedeutung ist die genetische Testung bei multifaktoriellen kardiovaskulären Volkskrankheiten. Biomarker haben dagegen das Potenzial, Individuen mit erhöhtem kardiovaskulärem Risiko zu identifizieren. Individualisierte, biomarkergeführte Therapien stellen eine attraktive Option für die Zukunft dar. Dafür ist die troponingesteuerte Therapie akuter Koronarsyndrome erfolgreiches Beispiel. Schließlich ist die individuelle Reaktion auf Arzneimittel teilweise genetisch determiniert und lässt sich mithilfe genetischer Analysen besser vorhersagen. Praktische Beispiele in der kardiovaskulären Medizin sind Warfarin und hohe Dosen von Simvastatin. Zusammengefasst werden personalisierte Ansätze in der kardiovaskulären Medizin sicher zunehmen. Dies erfordert die Entwicklung robusterer Methoden und Forschungen, die den tatsächlichen praktischen Nutzen der neuen Erkenntnisse auf den Prüfstand stellen.
Abstract
Improved therapy and prophylaxis of cardiovascular diseases have contributed to an increase in life expectancy like no other field of medicine. However, many cardiological diseases remain untreatable and standard therapies often work only in a minority of patients or cause more harm than benefit. Personalized approaches appear to be a promising solution. Monogenic heart diseases are paradigmatic for this approach and can in rare cases be treated mutation specifically. Overall, however, success remains limited. Next generation sequencing will facilitate the identification of mutations causing diseases. Cell culture models based on induced pluripotent stem cells open the perspective of individualized testing of disease severity and pharmacological or genetic therapy. In contrast to monogenic diseases genetic testing plays no practical role yet in the management of multifactorial cardiovascular diseases. Biomarkers can identify individuals with increased cardiovascular risk. Furthermore, biomarker-guided therapy represents an attractive option with troponin-guided therapy of acute coronary syndromes as a successful example. Individual responses to drugs vary and are partly determined by genes. Simple genetic analyses can improve response prediction and minimize side effects in cases such as warfarin and high doses of simvastatin. Taken together personalized approaches will gain importance in the cardiovascular field but this requires the development of better methods and research that quantifies the true value of the new knowledge.
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Eschenhagen, T., Blankenberg, S. Personalisierte Therapie in der Kardiologie. Internist 54, 147–154 (2013). https://doi.org/10.1007/s00108-012-3157-8
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DOI: https://doi.org/10.1007/s00108-012-3157-8
Schlüsselwörter
- Genotyp-Phänotyp-Korrelation
- Genotypbasierte Therapie
- Troponin
- Gentherapie
- Induzierte pluripotente Stammzellen