What is the clinical evidence from this study?

Population: Type 1 long QT syndrome (n=2). Intervention: ML277 vs. Baseline. Primary outcome: Action potential duration at 50% repolarization (APD50) in ms (p=<0.01).

March 18, 2015Stem Cell Research & TherapyOpen Access

Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes

Q: What are the key findings of this study?

The selective IKs activator ML277 significantly shortened action potential duration and reversed decreased IKs currents in patient-specific hiPSC-CMs with a novel KCNQ1 mutation.

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Key result

The selective IKs activator ML277 significantly shortened action potential duration and reversed decreased IKs currents in patient-specific hiPSC-CMs with a novel KCNQ1 mutation.

Why the study?

Does ML277 improve IKs current and action potential duration in LQT1 patient-specific hiPSC-CMs?

Population

Human induced pluripotent stem cell-derived cardiomyocytes generated from a type 1 long QT syndrome patient…

Comparison

ML277 (a selective IKs activator) vs Untreated baseline hiPSC-CMs and healthy control…

Design

Preclinical

Authors

DMDongrui MaBeihua University HWHeming WeiChina Academy of Chinese Medical Sciences JLJun LüShanghai University of Traditional Chinese Medicine

Discussion

Member takes

Implication

ML277 may merit further preclinical testing in LQT1; leaves open clinical translation.

Structured PICO

Does ML277 improve IKs current and action potential duration in LQT1 patient-specific hiPSC-CMs?

Population

Patient-specific human induced pluripotent stem cell-derived cardiomyocytes from a patient with type 1 long QT syndrome and her healthy father.

Intervention

ML277 (a selective IKs activator)

Comparator

Untreated baseline hiPSC-CMs and healthy control hiPSC-CMs

Outcome

Slowly activating delayed rectifier potassium channel (IKs) current amplitude and action potential duration (APD)surrogate

Main Result

Absolute Event Rate: 455.5% vs 601.1%

p-value: p=<0.01

The selective IKs activator ML277 successfully restored IKs function and shortened action potential duration in patient-specific hiPSC-CMs with a novel KCNQ1 mutation, highlighting its therapeutic potential for LQT1.

Limitations

Lack of IK1 current in hiPSC-CMs could alter cardiac ion currents and action potentials
Did not evaluate real-time contribution of cardiac ion currents concurrently with cardiac action potentials
Efficacy and safety of ML277 needs testing in animal models

Cite This Study

Ma et al. (2015) studied Type 1 long QT syndrome (n=2). ML277 vs. Baseline was evaluated on Action potential duration at 50% repolarization (APD50) in ms (p=<0.01). The selective IKs activator ML277 significantly shortened action potential duration and reversed decreased IKs currents in patient-specific hiPSC-CMs with a novel KCNQ1 mutation.

synapsesocial.com/papers/6a9b03821126ff10fc63bca7 https://doi.org/10.1186/s13287-015-0027-z

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Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider