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Biological auto-detection and termination of heart rhythm disturbances

Biological auto-detection and termination of heart rhythm disturbances

Objective

Imagine a heart that could no longer suffer from life-threatening rhythm disturbances, and not because of pills or traumatizing electroshocks from an Implantable Cardioverter Defibrillator (ICD) device. Instead, this heart has become able to rapidly detect & terminate these malignant arrhythmias fully on its own, after gene transfer. In order to explore this novel concept of biological auto-detection & termination of arrhythmias, I will investigate how forced expression of particular engineered proteins could i) allow cardiac tissue to become a detector of arrhythmias through rapid sensing of acute physiological changes upon their initiation. And how after detection, ii) this cardiac tissue (now as effector), could terminate the arrhythmia by generating a painless electroshock through these proteins.
To this purpose, I will first explore the requirements for such detection & termination by studying arrhythmia initiation and termination in rat models of atrial & ventricular arrhythmias using optical probes and light-gated ion channels. These insights will guide computer-based screening of proteins to identify those properties allowing effective arrhythmia detection & termination. These data will be used for rational engineering of the proteins with the desired properties, followed by their forced expression in cardiac cells and slices to assess anti-arrhythmic potential & safety. Promising proteins will be expressed in whole hearts to study their anti-arrhythmic effects and mechanisms, after which the most effective ones will be studied in awake rats.
This unexplored concept of self-resetting an acutely disturbed physiological state by establishing a biological detector-effector system may yield unique insight into arrhythmia management. Hence, this could provide distinctively innovative therapeutic rationales in which a diseased organ begets its own remedy, e.g. a Biologically-Integrated Cardiac Defibrillator (Bio-ICD).
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Host institution

ACADEMISCH ZIEKENHUIS LEIDEN

Address

Albinusdreef 2
2333 Za Leiden

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 485 028

Beneficiaries (1)

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ACADEMISCH ZIEKENHUIS LEIDEN

Netherlands

EU Contribution

€ 1 485 028

Project information

Grant agreement ID: 716509

Status

Ongoing project

  • Start date

    1 March 2017

  • End date

    28 February 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 485 028

  • EU contribution

    € 1 485 028

Hosted by:

ACADEMISCH ZIEKENHUIS LEIDEN

Netherlands