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.

Related Concept Videos

Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...