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Published on: September 27, 2013
Gene therapy for cardiovascular angiogenesis
Larry J Diaz-Sandoval1, Douglas W Losordo
1Divisions of Cardiovascular Medicine and Cardiovascular Research, St Elizabeth's Medical Center of Boston, Tufts University School of Medicine, 736 Cambridge St, Boston, MA 02135, USA.
Insights
Cardiovascular gene therapy using vascular endothelial growth factor shows promise for treating ischaemic heart disease and peripheral arterial disease. Further Phase III trials are needed to confirm its safety and efficacy in patients with unmet therapeutic needs.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
- Molecular Biology
Background:
- Atherosclerosis and endothelial dysfunction underpin cardiovascular disorders like ischaemic heart disease (IHD), a leading cause of death.
- Current treatments include pharmacotherapy, interventions, and surgery, but significant unmet needs remain for refractory cases.
Purpose of the Study:
- To evaluate the therapeutic potential of cardiovascular gene therapy (GT) with vascular endothelial growth factor (VEGF).
- To address unmet needs in treating IHD, peripheral arterial disease (PAD), restenosis, and neuropathies.
Main Methods:
- Preclinical studies and Phase I/II clinical trials investigating VEGF-based gene therapy.
- Assessment of improved perfusion and reduced ischaemia in models and patients.
Main Results:
- VEGF gene therapy demonstrated improved perfusion and reduced ischaemia in preclinical IHD models.
- Phase I and II trials indicated safety and therapeutic potential for IHD, PAD, restenosis, and neuropathies.
Conclusions:
- Cardiovascular gene therapy with VEGF shows promise for various ischaemic conditions.
- Phase III clinical trials are warranted to further validate the efficacy and safety of this approach.
Abstract:
Atherosclerosis and endothelial dysfunction are responsible for the pathophysiologic basis of the spectrum of cardiovascular disorders including ischaemic heart disease (IHD), the leading cause of morbidity and mortality in the US. There have been major advances, including the use of pharmacotherapy, coronary and peripheral percutaneous transluminal interventions (PTI), coronary and peripheral bypass surgery and primary/secondary prevention measures. There are, however, multiple unmet needs: IHD refractory to medical therapy and unsuitable for revascularisation; critical limb ischaemia unsuitable for PTI or surgery; restenosis; ischaemic/diabetic neuropathy and heart failure. Cardiovascular gene therapy (GT) with vascular endothelial growth factor (VEGF) has yielded improved perfusion and reduced ischaemia in preclinical models of IHD. Several preclinical studies and Phase I and II clinical trials have shown the safety and therapeutic potential of GT in the treatment of IHD, peripheral arterial disease (PAD), restenosis, and ischaemic and diabetic neuropathy, pointing to the need for Phase III clinical trials.
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