February 1, 2002Journal of Clinical Investigation

Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility

Q: What is the clinical evidence from this study?

Study design: Other. Population: Heart failure (model). Intervention: AdESERCA1-Kir2.1 (Dual gene therapy with SERCA1 and Kir2.1) vs. AdEGI (control vector). Primary outcome: Action potential duration at 90% repolarization (APD90) (p=<0.05).

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Key result

Dual gene therapy with SERCA1 and Kir2.1 significantly abbreviated action potential duration (220.1 vs 346.7 ms) and QTc interval without impairing left ventricular contractile function.

Why the study?

Does dual gene therapy with SERCA1 and Kir2.1 abbreviate excitation without depressing contraction in guinea pig hearts?

Population

Adult guinea pigs (220-260 g)

Comparison

Direct intramyocardial adenovirus injection of… vs Direct intramyocardial adenovirus injection of…

Design

Preclinical

Follow-up

72 hours

Authors

IEIrene L. EnnisCentro de Investigaciones Cardiovasculares RLRonald A. LiUniversity of Novi Sad AMAnne M. MurphyPediatric / Congenital Cardiology

Discussion

Member takes

Implication

Supports preclinical testing of dual gene therapy for heart failure arrhythmias; leaves open translation to clinical use.

Structured PICO

Does dual gene therapy with SERCA1 and Kir2.1 abbreviate excitation without depressing contraction in guinea pig hearts?

Population

Adult guinea pigs weighing 220-260 g subjected to intramyocardial injection of adenovirus vectors to evaluate dual gene therapy with SERCA1 and Kir2.1.

Intervention

Direct intramyocardial adenovirus injection of AdESERCA1-Kir2.1 (coexpressing calcium ATPase SERCA1 and potassium channel Kir2.1) along with AdCGI-DBEcR, followed by intraperitoneal injection of ecdysone receptor agonist GS-E

Comparator

Direct intramyocardial adenovirus injection of AdEGI (control vector) along with AdCGI-DBEcR, followed by intraperitoneal injection of ecdysone receptor agonist GS-E

Outcome

Action potential duration, intracellular Ca2+ transients, QTc interval, and echocardiographic contractile function at 72 hours post-injectionsurrogate

Main Result

Absolute Event Rate: 220.1% vs 346.7%

p-value: p=<0.05

Dual gene therapy coexpressing SERCA1 and Kir2.1 successfully abbreviates cardiac repolarization without impairing contractility in a guinea pig model, offering a potential strategy for treating arrhythmias in heart failure.

Limitations

The analysis is limited to characterizing the acute effects of transgene expression (72 hours).
It is unknown if endogenous gene expression is altered by acute overexpression or if it induces downstream stress or hypertrophic responses.
Low yield of viable infected myocytes (about 2%) due to limited efficiency of gene transduction by direct cardiac injection.
Limited to characterizing the acute effects of transgene expression
Did not probe whether endogenous gene expression is altered by acute overexpression or if it induces downstream stress or hypertrophic responses

Cite This Study

Ennis et al. (2002) studied Heart failure (model). AdESERCA1-Kir2.1 (Dual gene therapy with SERCA1 and Kir2.1) vs. AdEGI (control vector) was evaluated on Action potential duration at 90% repolarization (APD90) (p=<0.05). Dual gene therapy with SERCA1 and Kir2.1 significantly abbreviated action potential duration (220.1 vs 346.7 ms) and QTc interval without impairing left ventricular contractile function.

synapsesocial.com/papers/6a9de8a90bfbee156fd6ea16 https://doi.org/10.1172/jci0213359

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Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

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