Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models

Gal Aviel; Jacob Elkahal; Kfir Baruch Umansky; Hanna Bueno-Levy; Zachary Petrover; Yulia Kotlovski; Daria Lendengolts; David Kain; Tali Shalit; Lingling Zhang; Shoval Miyara; Matthias P. Kramer; Yifat Merbl; Stav Kozlovski; Ronen Alon; Rina Aharoni; Ruth Arnon; David Mishali; Uriel Katz; Dean Nachman; Rabea Asleh; Offer Amir; Eldad Tzahor; Rachel Sarig

doi:10.1038/s44161-024-00524-x

Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models

Gal Aviel
, Jacob Elkahal
, Kfir Baruch Umansky
, Hanna Bueno-Levy
, Zachary Petrover
, Yulia Kotlovski
, Daria Lendengolts
, David Kain
, Tali Shalit
, Lingling Zhang
, Shoval Miyara
, Matthias P. Kramer
, Yifat Merbl
, Stav Kozlovski
, Ronen Alon
, Rina Aharoni
, Ruth Arnon
, David Mishali
, Uriel Katz
, Dean Nachman

Rabea Asleh, Offer Amir, Eldad Tzahor^*, Rachel Sarig^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here, we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction and a rat model of ischemic HF. We provide mechanistic evidence indicating that, in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis. Overall, these findings highlight the potential repurposing of GA as a future therapy for a myriad of heart diseases.

Original language	English
Pages (from-to)	1049-1066
Number of pages	18
Journal	Nature Cardiovascular Research
Volume	3
Issue number	9
Early online date	26 Aug 2024
DOIs	https://doi.org/10.1038/s44161-024-00524-x
Publication status	Published - Sept 2024

Funding

We thank I. Sher and G. Brodsky from the Graphic Department at the Weizmann Institute for excellent graphic assistance, M. Cohen from the Histology Unit at the Weizmann Institute, Y. Levin and C. Katina from the Proteomic Unit of the Grand Israel National Center for Personalized Medicine at the Weizmann Institute and O. Vazhgovsky for coordinating the biopsy transfer from Sheba Medical Center. The study was supported by the following funding sources: the European Research Council, ERC AdG grant 788194, CardHeal (E.T.), ERC-PoC 899224, ReDHeaD (E.T.), EU Horizon 2020 Research and Innovation Programme REANIMA (grant 874764) (E.T.), ERA-CVD CARDIO-PRO, the Israel Science Foundation (grant 2214/22) (E.T. and R.S.), the Yotam Project and the Weizmann Institute Sustainability and Energy Research Initiative (grant 142735), the Minerva Center on ‘Aging, from physical materials to human tissues’, the Israel Ministry of Science and Technology, the Estate of Caroline Cancelmo, the Erica Drake Fund, the Weizmann UK Building for Biocomplexity Research (GG 2016), the Aharon and Tova (Buena) Cohen Memorial Fund, the Horwitz Research Fund, the Yacov Chaoul Kapczuk Fund, the Estate of Elizabeth Wachsman, Seed for Peace, the Jacques Asseoff Trust, the Gurwin Family Fund for Scientific Research, the Midwest Electron Microscope Project and the Israel Science Foundation (1703/22) (R. Alon). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The illustration in Fig. 2a was created with BioRender. Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2024.

All Science Journal Classification (ASJC) codes

Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cardiology and Cardiovascular Medicine
Cell Biology

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10.1038/s44161-024-00524-x

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Aviel, G., Elkahal, J., Umansky, K. B., Bueno-Levy, H., Petrover, Z., Kotlovski, Y., Lendengolts, D., Kain, D., Shalit, T., Zhang, L., Miyara, S., Kramer, M. P., Merbl, Y., Kozlovski, S., Alon, R., Aharoni, R., Arnon, R., Mishali, D., Katz, U., ... Sarig, R. (2024). Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models. Nature Cardiovascular Research, 3(9), 1049-1066. https://doi.org/10.1038/s44161-024-00524-x

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title = "Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models",

abstract = "Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here, we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction and a rat model of ischemic HF. We provide mechanistic evidence indicating that, in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis. Overall, these findings highlight the potential repurposing of GA as a future therapy for a myriad of heart diseases.",

author = "Gal Aviel and Jacob Elkahal and Umansky, \{Kfir Baruch\} and Hanna Bueno-Levy and Zachary Petrover and Yulia Kotlovski and Daria Lendengolts and David Kain and Tali Shalit and Lingling Zhang and Shoval Miyara and Kramer, \{Matthias P.\} and Yifat Merbl and Stav Kozlovski and Ronen Alon and Rina Aharoni and Ruth Arnon and David Mishali and Uriel Katz and Dean Nachman and Rabea Asleh and Offer Amir and Eldad Tzahor and Rachel Sarig",

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Aviel, G, Elkahal, J , Umansky, KB, Bueno-Levy, H, Petrover, Z, Kotlovski, Y, Lendengolts, D, Kain, D, Shalit, T, Zhang, L , Miyara, S , Kramer, MP , Merbl, Y, Kozlovski, S, Alon, R , Aharoni, R , Arnon, R, Mishali, D, Katz, U, Nachman, D, Asleh, R, Amir, O, Tzahor, E & Sarig, R 2024, 'Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models', Nature Cardiovascular Research, vol. 3, no. 9, pp. 1049-1066. https://doi.org/10.1038/s44161-024-00524-x

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AU - Aviel, Gal

AU - Elkahal, Jacob

AU - Umansky, Kfir Baruch

AU - Bueno-Levy, Hanna

AU - Petrover, Zachary

AU - Kotlovski, Yulia

AU - Lendengolts, Daria

AU - Kain, David

AU - Shalit, Tali

AU - Zhang, Lingling

AU - Miyara, Shoval

AU - Kramer, Matthias P.

AU - Merbl, Yifat

AU - Kozlovski, Stav

AU - Alon, Ronen

AU - Aharoni, Rina

AU - Arnon, Ruth

AU - Mishali, David

AU - Katz, Uriel

AU - Nachman, Dean

AU - Asleh, Rabea

AU - Amir, Offer

AU - Tzahor, Eldad

AU - Sarig, Rachel

PY - 2024/9

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N2 - Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here, we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction and a rat model of ischemic HF. We provide mechanistic evidence indicating that, in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis. Overall, these findings highlight the potential repurposing of GA as a future therapy for a myriad of heart diseases.

AB - Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here, we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction and a rat model of ischemic HF. We provide mechanistic evidence indicating that, in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis. Overall, these findings highlight the potential repurposing of GA as a future therapy for a myriad of heart diseases.

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SN - 2731-0590

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SP - 1049

EP - 1066

JO - Nature Cardiovascular Research

JF - Nature Cardiovascular Research

IS - 9

ER -

Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models

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