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[Gene therapy with VEGF]
L Maillard1, P Peycher, O Fichaux
1Laboratoire de Biotechnologie et Génétique expérimentale, CHU Trousseau, Tours. luc.maillard@med.univ-tours.fr
Unlabelled:
NEW THERAPEUTIC OPTION: Atherosclerosis-related conditions are the primary cause of mortality in western countries. The incidence of severe limb-threatening ischemia of the lower limbs reaches 500 to 1000 per million inhabitants. The lack of effective treatment capable of preventing amputation in the most severe cases has led to research into the development of collateral circulation to replace the occluded arteries. Preclinical data has demonstrated that angiogenic factors can stimulate collateral circulation. This new therapeutic approach is called "angiogenesis therapy". VEGF: Vascular endothelial growth factor (VEGF) is a DNA fragment coding for a protein that has raised great expectations which are now entering the era of reality. Several administration routes are possible. The DNA fragments can be deposited on the arterial wall using a catheter. The hydrogel balloon operates like an angioplasty balloon covered with a hydrophilic layer which delivers the DNA fragments when inflated. More recently, the intramuscular route has been used to take advantage of the vascular distribution of this angiogenic cytokine. The peripheral muscle cells can perform the transformation via transcription to a messenger RNA for translation into the human DNA protein. A real application of gene therapy.
Perspectives:
Undeniable clinical benefit observed in the limited number of patients treated has led to proposing angiogenic cytokines for the treatment of ischemic heart disease when angioplasty or bypass surgery. The most recent series are small, but show that intramyocardial injection of VEGF is feasible. Larger randomized series will evaluate these techniques. Despite the large body of preclinical data, many questions remain unanswered.
Insights
New gene therapy using vascular endothelial growth factor (VEGF) shows promise for treating severe limb ischemia by stimulating new blood vessel growth. This angiogenesis therapy offers a potential alternative to amputation.
Area of Science:
- Cardiovascular Research
- Gene Therapy
- Regenerative Medicine
Background:
- Atherosclerosis leads to lower limb ischemia, a major cause of mortality and amputation.
- Current treatments for severe limb ischemia are limited, necessitating new therapeutic strategies.
- Angiogenesis therapy, stimulating new blood vessel formation, is a promising approach.
Purpose of the Study:
- To explore the potential of vascular endothelial growth factor (VEGF) as a therapeutic agent for angiogenesis.
- To evaluate different administration routes for VEGF gene therapy.
- To assess the feasibility and efficacy of VEGF in promoting collateral circulation.
Main Methods:
- Delivery of DNA fragments encoding VEGF via catheter-based hydrogel balloons to arterial walls.
- Intramuscular administration of VEGF gene therapy to leverage muscle cell protein synthesis.
- Preclinical studies demonstrating VEGF's ability to stimulate collateral circulation.
Main Results:
- Preclinical data supports VEGF's role in stimulating collateral circulation.
- Intramuscular VEGF gene therapy utilizes peripheral muscle cells for protein production.
- Early clinical observations suggest feasibility and potential benefit in limited patient cohorts.
Conclusions:
- Angiogenic cytokines like VEGF show potential for treating ischemic conditions.
- Intramyocardial VEGF injection is feasible, with ongoing larger trials planned.
- Further research is needed to address remaining questions despite promising preclinical data.