Design of a Phase 1/2 Trial of Intracoronary Administration of AAV1/SERCA2a in Patients With Heart Failure

Hajjar, Roger J.; Zsebo, Krisztina M.; Deckelbaum, Lawrence I.; Thompson, Craig; Rudy, Jeff; Yaroshinsky, Alex; Ly, Hung Q.; Kawase, Yoshiaki; Wagner, Kim; Borow, Kenneth; Jaski, Brian E.; London, Barry; Greenberg, Barry; Pauly, Daniel F.; Patten, Richard D.; Starling, Randall C.; Mancini, Donna; Jessup, Mariell

doi:10.1016/j.cardfail.2008.02.005

Cited by 199 publications

(181 citation statements)

References 55 publications

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“…A 12-month follow-up of these patients showed an acceptable safety profile. 16,50 Improvement was detected in several patients, reflected by symptomatic (five patients), functional (four patients), biomarker (two patients) and left ventricle function/remodeling (six patients) parameters. Although this was a phase 1 study involving a small number of patients, early results found that AAV1.SERCA2a treatment conferred quantitative biological benefit.…”

Section: Serca2a Gene Therapymentioning

confidence: 99%

“…16,50 CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease) is a multicenter trial designed to evaluate the safety profile and the biological effects of gene transfer of the SERCA2a complimentary DNA by delivering a rAAV1 (AAV1.SERCA2a) in patients with advanced HF. Participants in this trial were administered a single intracoronary infusion of AAV1.SERCA2a in an open-label approach.…”

Section: Serca2a Gene Therapymentioning

confidence: 99%

“…Participants in this trial were administered a single intracoronary infusion of AAV1.SERCA2a in an open-label approach. 16,50 Cohorts 1-4 of three patients each received sequentially a single escalating dose of AAV1.SERCA2a. A 12-month follow-up of these patients showed an acceptable safety profile.…”

Section: Serca2a Gene Therapymentioning

confidence: 99%

See 2 more Smart Citations

Sarcoplasmic reticulum and calcium cycling targeting by gene therapy

Hulot

Senyei

2012

Gene Ther

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Although progress in conventional treatments is making steady and incremental gains to reduce mortality associated with heart failure (HF), there remains a need to explore potentially new therapeutic approaches. HF induced by different etiologies such as coronary artery disease, hypertension, diabetes, infection or inflammation results generally in calcium cycling dysregulation at the myocyte level. Recent advances in understanding of the molecular basis of these calcium cycling abnormalities, together with the evolution of increasingly efficient gene transfer technology, has placed HF within the reach of gene-based therapy. Furthermore, the recent successful completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium pump ushers in a new era for gene therapy for the treatment of HF.

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Section: Serca2a Gene Therapymentioning

confidence: 99%

Section: Serca2a Gene Therapymentioning

confidence: 99%

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Sarcoplasmic reticulum and calcium cycling targeting by gene therapy

Hulot

Senyei

2012

Gene Ther

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“…The latter therapy, though increasingly effective, is compromised by severe complications, and a 1-year mortality rate of 20 % [7]. Gene therapy of sarcoplasmic reticulum ATPase (CUPID trial [8,9]; NCT01643330, NCT00534703) is currently being developed as a novel treatment option for patients with heart failure, but is unlikely to be effective in patients in whom a critical fraction of contractile mass is lost. These patients are the target population for regenerative approaches, i.e., attempts to add new contractile heart muscle mass to the failing heart.…”

Section: Introductionmentioning

confidence: 99%

Engineering Cardiovascular Regeneration

et al. 2015

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The human heart has very limited regenerative capacity, making the loss of heart muscle tissue during myocardial infarction essentially irreversible. Regenerative medicine aims at promoting the formation of new functional heart muscle in an injured heart, either by stimulating myocyte proliferation, formation of myocytes from preexisting stem cells, direct reprogramming of fibroblasts into myocytes, or adding new muscle tissue from exogenous stem cell sources. Recent advances in stem cell research make these goals more realistic. This review provides a short overview about different approaches for cardiovascular regeneration, stem cell sources, and modes of application, focusing on current cardiac tissue engineering techniques and their way towards clinical application.

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“…However, large randomized studies failed to corroborate these results (26), with the consequence that clinical gene-therapy studies with the goal to improve cardiac vascularization have been abandoned. In the field of chronic CHF, a long trajectory of preclinical experimentation by many groups has resulted in the recent initiation of the first clinical study of viral vector-based gene transfer for CHF (45).…”

mentioning

confidence: 99%