PHOTOHEART PROJECT EXPLAINED
PHOTOHEART IN A NUTSHELL
A common treatment after a heart attack is the reopening of the blocked coronary artery to restore the blood flow. This is what experts call reperfusion therapy, which has greatly reduced mortality of patients. However, many survivors end up with large infarct areas that compromise cardiac function in the long-term.
The PhotoHeart project aims to provide early and localized treatment at the time of reperfusion therapy to significantly reduce cardiac tissue damage, thus boosting patient recovery and minimizing future cardiac conditions. To this end, the MCS team led by Amadeu Llebaria, from IQAC-CSIC, in collaboration with teams from VHIR and Johns Hopkins University, is developing a photopharmacological therapy that will allow light-controlled drugs to be administered and only activated in the area most affected by reperfusion therapy by attaching a light device to the catheter used to open the arteries.
The goals of the project are:
The in vivo assessment of the light delivery catheters in explanted farm adult pig hearts as well as the validation of the system efficacy during reperfusion in a pig model.
PAST EVENT – Light switching molecules: Advancing pharmacology for heart and neural diseases
This R+D+I meeting will brought together researchers, entrepreneurs and the pharma industry interested in photopharmacology research, as well as in the transfer of research results to the market and the development of associated medical devices.
When: March 3, 2023
Where: Auditorium of the Museo de la Ciencia CosmoCaixa (Barcelona).
Read the programme here.
HOW DOES THE PROPOSED TREATMENT WORK?
THE PHOTOHEART TIMELINE
Oct. 2021 - Dec. 2023
NCX inhibitors: design and in vitro validation
Design of molecules that can inhibit NCX channels upon light activation. Optimization of their physical, photochemical and biological properties to control the reversible isomerization induced by light. Determination of their pharmacological parameters in cells expressing NCX.
Teams involved: IQAC-CSIC
Oct. 2021 - Dec. 2023
Design and construction of catheters
Design of intracoronary catheters containing an illumination system to obtain the activation/deactivation of light-controlled NCX inhibitors. Setting the light control system and light sources to be employed. Construction of catheter prototypes.
Teams involved: JHU
Oct. 2021 - Dec. 2023
Apr. 2022 - Dec. 2023
In vitro cardiomyocyte assay
Study of the physiologic effects of NCX inhibition in cardiomyocyte cell cultures. Establishment of the optimal duration of NCX inhibition in experimental conditions of simulated ischemia and reperfusion.
Teams involved: VHIR, IQAC-CSIC, JHU
Oct. 2022 - Mar. 2024
Ex vivo pig assay
Assessment of intracardiac catheters and light parameters in an ex vivo pig model that reproduces the clinical conditions of a coronary angioplasty. Evaluation of the effectiveness of the overall system: check of the temporary inhibition of NCX only at the ischemic sites.
Teams involved: VHIR, IQAC-CSIC, JHU
Oct. 2022 - Mar. 2024
Apr. 2022 - Dec. 2023
In vitro cardiomyocyte assay
Study of the physiologic effects of NCX inhibition in cardiomyocyte cell cultures. Establishment of the optimal duration of NCX inhibition in experimental conditions of simulated ischemia and reperfusion.
Teams involved: VHIR, IQAC-CSIC, JHU
Apr. 2023 - Feb. 2025
In vivo pig assay
Validation of the protocol first in an open-heart pig model and then in a closed-chest pig model of infarction. The light-controlled NCX inhibitor will be administered at the end of the ischemic period, and the light device-equipped catheter will be advanced beyond the occlusion site upon coronary reperfusion.
Teams involved: VHIR, IQAC-CSIC, JHU
Apr. 2023 - Feb. 2025
AN INTERNATIONAL COLLABORATION
Project leader
Dr. Amadeu Llebaria
Medicinal Chemistry & Synthesis group (MCS)
Institut de Química Avançada de Catalunya, IQAC-CSIC
Team: Jorge Gandia, Juanlo Catena, Xavier Rovira, Elisabet Perez
Co-PI
Dr. Javier Inserte
Cardiovascular Diseases
Fundació Hospital Universitari Vall d’Hebron – Institut de Recerca (VHIR)
Team: Marisol Ruiz-Meana, Antonio Rodriguez-Sinovas, Neus Bellera, José A. Barrabés, Diana Bou-Teen
Co-PI
Dr. Pedro Irazoqui
Electrical and Computer Engineering Dept.
Johns Hopkins Whiting School of Engineering (JHU)