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VEGF gene therapy for coronary artery disease and peripheral vascular disease
Henrik Sandvad Rasmussen1, Camilla Sandvad Rasmussen, Jennifer Macko
1GenVec Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20878, USA. hrasmussen@genvec.com
Insights
BIOBYPASS, a gene therapy using vascular endothelial growth factor (VEGF), shows promise for treating severe coronary artery disease (CAD) and peripheral vascular disease (PVD). Early clinical trials indicate it is well-tolerated and may improve blood vessel formation in patients ineligible for surgery.
Area of Science:
- Cardiovascular Medicine
- Gene Therapy
- Regenerative Medicine
Background:
- Coronary artery disease (CAD) and peripheral arterial disease (PAD) pose significant global health challenges.
- Despite advancements, many patients with severe CAD/PAD remain symptomatic and unsuitable for revascularization.
- Therapeutic angiogenesis offers a novel treatment avenue for these patients.
Purpose of the Study:
- To review the rationale and preclinical/clinical data for Ad(GV)VEGF121.10 (BIOBYPASS) as a therapeutic angiogenesis agent.
- To evaluate the potential of gene therapy with vascular endothelial growth factor (VEGF) for treating ischemic vascular diseases.
Main Methods:
- Review of preclinical studies demonstrating the angiogenic activity of BIOBYPASS.
- Summary of Phase I clinical trial data on the safety and tolerability of BIOBYPASS in patients with severe CAD and peripheral vascular disease (PVD).
Main Results:
- Preclinical studies confirmed the angiogenic (blood vessel-forming) capacity of BIOBYPASS, both anatomically and functionally.
- Phase I trials indicated that intramyocardial and intramuscular delivery of BIOBYPASS was well-tolerated in patients with severe CAD and PVD.
- Early clinical data suggested potential therapeutic activity, prompting Phase II trials.
Conclusions:
- BIOBYPASS, an adenovector encoding VEGF(121), is a promising candidate for therapeutic angiogenesis.
- Early clinical evidence supports the safety and potential efficacy of BIOBYPASS for patients with severe ischemic vascular conditions.
- Further investigation in Phase II "proof-of-concept" studies is warranted.
Abstract:
Coronary artery disease (CAD) and peripheral arterial disease (PAD) are significant medical problems worldwide. Although substantial progress has been made in prevention as well as in the treatment, particularly of CAD, there are a large number of patients, who despite maximal medical treatment have substantial symptomatology and who are not candidates for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing treatment option. Ad(GV)VEGF121.10 (BIOBYPASS) is an adenovector, carrying the transgene encoding for human vascular endothelial growth factor 121 (VEGF(121)). A number of preclinical studies have demonstrated angiogenic activity of BIOBYPASS, not only anatomically but also functionally. Phase I clinical studies have demonstrated that intramyocardial infection of BIOBYPASS in patients with severe CAD as well as intramuscular injections of BIOBYPASS in patients with severe peripheral vascular disease (PVD) was well tolerated; furthermore, these studies provided some intriguing indications of activity, which led to initiation of major randomized Phase II "proof-of-concept" studies. This paper provides a review of the rationale behind BIOBYPASS as well as a summary of pertinent preclinical and early clinical data.