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Angiogenic gene therapy in cardiovascular diseases: dream or vision?
Seppo Ylä-Herttuala1,2, Charles Bridges3, Michael G Katz3
1Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio 70211, Finland.
Insights
New gene therapy strategies are needed for chronic cardiovascular diseases. Current approaches show limited clinical success, necessitating improved gene transfer and targeted delivery for better patient outcomes.
Area of Science:
- Cardiovascular Medicine
- Gene Therapy
- Regenerative Medicine
Background:
- Chronic cardiovascular diseases pose significant health challenges.
- Current treatments are insufficient for up to 30% of patients, highlighting the need for novel therapeutic strategies.
- Gene therapy and therapeutic vascular growth represent promising new treatment avenues.
Purpose of the Study:
- To review recent advances in gene therapy for cardiovascular diseases.
- To re-evaluate angiogenic therapy as a standalone treatment.
- To explore the potential of combining therapies for improved clinical benefits.
Main Methods:
- Review of clinical trials involving growth factors (e.g., VEGF, FGF, HGF).
- Analysis of challenges in gene therapy, including transfer efficiency and expression duration.
- Discussion of improvements in study protocols, vector delivery, and patient selection.
Main Results:
- Previous trials demonstrated increased vascularity but limited clinical significance.
- Identified challenges in gene therapy include efficiency, expression longevity, endpoint selection, and patient suitability.
- Ongoing trials incorporate enhanced protocols, delivery systems, and growth factors.
Conclusions:
- Angiogenic therapy alone may be insufficient for optimal tissue function.
- Combining gene therapy with regenerative medicine or revascularization may enhance clinical benefits.
- Further research and improved strategies are crucial for effective cardiovascular disease treatment.
Abstract:
Chronic cardiovascular diseases are significant health problems. Although current treatment strategies have tremendously improved disease management, up to 30% of these patients cannot be successfully treated with current treatment approaches and new treatment strategies are clearly needed. Gene therapy and therapeutic vascular growth may provide a new treatment option for these patients. Several growth factors, like vascular endothelial growth factors, fibroblast growth factors and hepatocyte growth factor have been tested in clinical trials. However, apart from demonstration of increased vascularity, very few results with clinical significance have been obtained. Problems with gene transfer efficiency, short duration of transgene expression, selection of endpoints, and suboptimal patients for gene therapy have been recognized. Ongoing gene therapy trials have included improvements in study protocols, vector delivery and endpoints, addressing the identified problems. Better, targeted delivery systems and new, more optimal growth factors have been taken to clinical testing. Recent advances in these areas will be discussed and the concept of angiogenic therapy as a sole treatment is re-evaluated. A combination with regenerative therapies or standard revascularization operations might be needed to improve tissue function and clinical benefits.
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