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Updated: Oct 19, 2025
Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart
Published on: September 2, 2021
Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart
Henna Korpela1, Satu Siimes1, Seppo Ylä-Herttuala2
1A.I. Virtanen Institute, University of Eastern Finland.
Insights
This study presents a large animal model for evaluating gene therapy in ischemic heart disease. The model uses pigs to assess therapeutic angiogenesis, aiming for better clinical trial predictability.
Area of Science:
- Cardiovascular Research
- Gene Therapy
- Animal Models
Background:
- Coronary artery disease (CAD) remains a leading cause of death and symptoms, with current treatments often insufficient.
- Gene therapy for therapeutic angiogenesis offers a promising new approach for improving blood flow and alleviating symptoms in CAD patients.
- Translating myocardial gene therapy from laboratory research to clinical application requires robust evaluation in suitable animal models.
Purpose of the Study:
- To introduce a large animal model for assessing gene therapy efficacy in ischemic porcine hearts.
- To mimic chronic coronary artery disease and induce therapeutic angiogenesis in hypoxic cardiac regions.
- To evaluate the safety and efficacy of gene therapy using clinically relevant endpoints.
Main Methods:
- Development of a porcine model to simulate chronic coronary artery disease.
- Utilization of electroanatomical mapping for precise gene transfer targeting.
- Application of advanced imaging techniques, including ultrasound and 15H2O-PET, for efficacy assessment.
Main Results:
- The developed porcine model successfully mimics chronic ischemic heart conditions.
- The model allows for targeted gene delivery to induce therapeutic angiogenesis.
- Clinically relevant imaging methods enable comprehensive safety and efficacy evaluation.
Conclusions:
- This large animal model provides a valuable platform for preclinical evaluation of gene therapies for coronary artery disease.
- The model's ability to replicate disease conditions and utilize clinical endpoints enhances the predictability of clinical trial outcomes.
- Further research using this model can accelerate the bench-to-bedside translation of novel gene therapies for myocardial ischemia.
Abstract:
Coronary artery disease is one of the significant causes of mortality and morbidity worldwide. Despite the progression of current therapeutics, a considerable proportion of coronary artery disease patients remain symptomatic. Gene therapy-mediated therapeutic angiogenesis offers a novel therapeutic method for improving myocardial perfusion and relieving symptoms. Gene therapy with different angiogenic factors has been studied in few clinical trials. Due to the novelty of the method, the progress of myocardial gene therapy is a continuous path from bench to bedside. Therefore, large animal models are needed for evaluating the safety and efficacy. The more the large animal model identifies the original disease and the endpoints used in clinics, the more predictable outcomes are from clinical trials. Here, we introduce a large animal model for evaluating the efficacy of the gene therapy in the ischemic porcine heart. We use clinically relevant imaging methods such as ultrasound imaging and 15H2O-PET. For targeting the gene transfers into the desired area, electroanatomical mapping is used. The aim of this method is: (1) to mimic chronic coronary artery disease, (2) to induce therapeutic angiogenesis at hypoxic areas of the heart, and (3) to evaluate the safety and efficacy of the gene therapy by using relevant endpoints.
