Elamipretide - Revision history

Dmitry Dzhagarov at 12:26, 29 March 2023

2023-03-29T12:26:40Z

← Older revision		Revision as of 12:26, 29 March 2023
Line 1:		Line 1:
	'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small cell-permeable tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.<ref>Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136 DOI: 10.1007/s11095-011-0476-8</ref> SS-31 binds selectively to cardiolipin that prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron carrying function. This optimizes mitochondrial electron transport and ATP synthesis and prevents ROS production at the electron transport chain.<ref>Birk, A. V., Chao, W. M., Bracken, C., Warren, J. D., & Szeto, H. H. (2014). Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. British journal of pharmacology, 171(8), 2017-2028. PMID: 24134698 PMCID: PMC3976619 DOI: 10.1111/bph.12468</ref> As a result, SS-31 protects the structure of mitochondrial cristae and promotes oxidative phosphorylation. SS-31 represents a class of compounds that can recharge the cellular powerhouse and restore bioenergetics.<ref>Szeto, H. H. (2014). First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British journal of pharmacology, 171(8), 2029-2050. PMID: 24117165 PMCID: PMC3976620 DOI: 10.1111/bph.12461</ref>		'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small cell-permeable tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.<ref>Zhao, K., Zhao, G. M., Wu, D., Soong, Y., Birk, A. V., Schiller, P. W., & Szeto, H. H. (2004). Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. The Journal of biological chemistry, 279(33), 34682-34690. PMID: 15178689 DOI: 10.1074/jbc.M402999200</ref><ref>Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136 DOI: 10.1007/s11095-011-0476-8</ref> SS-31 binds selectively to cardiolipin that prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron carrying function. This optimizes mitochondrial electron transport and ATP synthesis and prevents ROS production at the electron transport chain.<ref>Birk, A. V., Chao, W. M., Bracken, C., Warren, J. D., & Szeto, H. H. (2014). Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. British journal of pharmacology, 171(8), 2017-2028. PMID: 24134698 PMCID: PMC3976619 DOI: 10.1111/bph.12468</ref> As a result, SS-31 protects the structure of mitochondrial cristae and promotes oxidative phosphorylation. SS-31 represents a class of compounds that can recharge the cellular powerhouse and restore bioenergetics.<ref>Szeto, H. H. (2014). First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British journal of pharmacology, 171(8), 2029-2050. PMID: 24117165 PMCID: PMC3976620 DOI: 10.1111/bph.12461</ref>

	Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>		Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>
Line 7:		Line 7:
	In animal models of myocardial infarction and ischemia–reperfusion injury elamipretide yielded promising results, showing reduced infarct size and improved left ventricular (LV) contractile function,<ref>Dai, W., Shi, J., Gupta, R. C., Sabbah, H. N., Hale, S. L., & Kloner, R. A. (2014). Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats. Journal of cardiovascular pharmacology, 64(6), 543-553. PMID: 25165999 DOI: 10.1097/FJC.0000000000000155</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref><ref>Werbner, B., Tavakoli-Rouzbehani, O. M., Fatahian, A. N., & Boudina, S. (2023). The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure. The journal of cardiovascular aging, 3(1). PMID: 36742465 PMCID: PMC9894375 DOI: 10.20517/jca.2022.42</ref><ref>Brown, D. A., Hale, S. L., Baines, C. P., Rio, C. L. D., Hamlin, R. L., Yueyama, Y., ... & Kloner, R. A. (2014). Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. Journal of cardiovascular pharmacology and therapeutics, 19(1), 121-132. PMID: 24288396 PMCID: PMC4103197 DOI: 10.1177/1074248413508003</ref> in particular by suppressing cardiac fibrosis in the border zone of the infarcted heart,<ref>Shi, J., Dai, W., Hale, S. L., Brown, D. A., Wang, M., Han, X., & Kloner, R. A. (2015). Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart. Life sciences, 141, 170-178. PMID: 26431885 PMCID: PMC4973309 DOI: 10.1016/j.lfs.2015.09.022</ref>		In animal models of myocardial infarction and ischemia–reperfusion injury elamipretide yielded promising results, showing reduced infarct size and improved left ventricular (LV) contractile function,<ref>Dai, W., Shi, J., Gupta, R. C., Sabbah, H. N., Hale, S. L., & Kloner, R. A. (2014). Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats. Journal of cardiovascular pharmacology, 64(6), 543-553. PMID: 25165999 DOI: 10.1097/FJC.0000000000000155</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref><ref>Werbner, B., Tavakoli-Rouzbehani, O. M., Fatahian, A. N., & Boudina, S. (2023). The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure. The journal of cardiovascular aging, 3(1). PMID: 36742465 PMCID: PMC9894375 DOI: 10.20517/jca.2022.42</ref><ref>Brown, D. A., Hale, S. L., Baines, C. P., Rio, C. L. D., Hamlin, R. L., Yueyama, Y., ... & Kloner, R. A. (2014). Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. Journal of cardiovascular pharmacology and therapeutics, 19(1), 121-132. PMID: 24288396 PMCID: PMC4103197 DOI: 10.1177/1074248413508003</ref> in particular by suppressing cardiac fibrosis in the border zone of the infarcted heart,<ref>Shi, J., Dai, W., Hale, S. L., Brown, D. A., Wang, M., Han, X., & Kloner, R. A. (2015). Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart. Life sciences, 141, 170-178. PMID: 26431885 PMCID: PMC4973309 DOI: 10.1016/j.lfs.2015.09.022</ref>

	However, elamipretide has failed to show promising results in clinical trials in patients with various heart failure phenotypes ([https://www.clinicaltrials.gov/ct2/history/NCT02814097 NCT02814097], [https://www.clinicaltrials.gov/ct2/history/NCT02914665 NCT02914665], [https://www.clinicaltrials.gov/ct2/history/NCT02788747 NCT02788747]).		However, elamipretide has failed to show promising results in clinical trials in patients with various heart failure phenotypes ([https://www.clinicaltrials.gov/ct2/history/NCT02814097 NCT02814097], [https://www.clinicaltrials.gov/ct2/history/NCT02914665 NCT02914665], [https://www.clinicaltrials.gov/ct2/history/NCT02788747 NCT02788747]). This could be explained by the quick degradation of the peptide in the bloodstream, although some modifications have been made to reduce the degradation of this peptide, such as a switch from an L-amino acid to a D-amino acid in the first position to make it resistant to aminopeptidase activity and a C-terminal amidation to reduce hydrolysis.<ref name="Two"/> In addition it has been developed bioconjugates of elamipretide to form elamipretide decorated nanoparticles.<ref>Gendron, A., Domenichini, S., Zanna, S., Gobeaux, F., Piesse, C., Desmaële, D., & Varna, M. (2023). Development and Characterization of Innovative Multidrug Nanoformulation for Cardiac Therapy. Materials, 16(5), 1812. PMID: 36902927 PMCID: PMC10003764 DOI: 10.3390/ma16051812</ref>

	Elamipretide has also improved mitochondrial function in kidneys in large animal studies.<ref>Zhu, Y., Luo, M., Bai, X., Li, J., Nie, P., Li, B., & Luo, P. (2022). SS-31, a mitochondria-targeting peptide, ameliorates kidney disease. Oxidative Medicine and Cellular Longevity, 2022. PMID: 35707274 PMCID: PMC9192202 DOI: 10.1155/2022/1295509</ref>		Elamipretide has also improved mitochondrial function in kidneys in large animal studies.<ref>Zhu, Y., Luo, M., Bai, X., Li, J., Nie, P., Li, B., & Luo, P. (2022). SS-31, a mitochondria-targeting peptide, ameliorates kidney disease. Oxidative Medicine and Cellular Longevity, 2022. PMID: 35707274 PMCID: PMC9192202 DOI: 10.1155/2022/1295509</ref>

Dmitry Dzhagarov at 20:45, 28 March 2023

2023-03-28T20:45:51Z

← Older revision		Revision as of 20:45, 28 March 2023
Line 3:		Line 3:
	Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>		Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>
	.Treatment with SS-31 SS-31 reversed age-related decline in maximum mitochondrial ATP production (ATPmax) and coupling of oxidative phosphorylation (P/O); restores redox homeostasis, improves mitochondrial quality, and increases exercise tolerance in aged mice without an increase in mitochondrial content.<ref>Campbell, M. D., Duan, J., Samuelson, A. T., Gaffrey, M. J., Merrihew, G. E., Egertson, J. D., ... & Marcinek, D. J. (2019). Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radical Biology and Medicine, 134, 268-281. PMID: 30597195 PMCID: PMC6588449 DOI: 10.1016/j.freeradbiomed.2018.12.031</ref><ref>Siegel, M. P., Kruse, S. E., Percival, J. M., Goh, J., White, C. C., Hopkins, H. C., ... & Marcinek, D. J. (2013). Mitochondrial‐targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging cell, 12(5), 763-771.		.Treatment with SS-31 SS-31 reversed age-related decline in maximum mitochondrial ATP production (ATPmax) and coupling of oxidative phosphorylation (P/O); restores redox homeostasis, improves mitochondrial quality, and increases exercise tolerance in aged mice without an increase in mitochondrial content.<ref>Campbell, M. D., Duan, J., Samuelson, A. T., Gaffrey, M. J., Merrihew, G. E., Egertson, J. D., ... & Marcinek, D. J. (2019). Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radical Biology and Medicine, 134, 268-281. PMID: 30597195 PMCID: PMC6588449 DOI: 10.1016/j.freeradbiomed.2018.12.031</ref><ref>Siegel, M. P., Kruse, S. E., Percival, J. M., Goh, J., White, C. C., Hopkins, H. C., ... & Marcinek, D. J. (2013). Mitochondrial‐targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging cell, 12(5), 763-771.
	PMID: 23692570 PMCID: PMC3772966 DOI: 10.1111/acel.12102</ref><ref>Campbell, M. D., Samuelson, A. T., Chiao, Y. A., Sweetwyne, M. T., Ladiges, W. C., Rabinovitch, P. S., & Marcinek, D. J. (2023). Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice. GeroScience, 1-11. PMID: 36840897 DOI: 10.1007/s11357-023-00754-0</ref>		PMID: 23692570 PMCID: PMC3772966 DOI: 10.1111/acel.12102</ref><ref>Campbell, M. D., Samuelson, A. T., Chiao, Y. A., Sweetwyne, M. T., Ladiges, W. C., Rabinovitch, P. S., & Marcinek, D. J. (2023). Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice. GeroScience, 1-11. PMID: 36840897 DOI: 10.1007/s11357-023-00754-0</ref><ref>Nickel, K., Zhu, L., Mangalindan, R., Snyder, J. M., Tucker, M., Whitson, J., ... & Ladiges, W. (2022). Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice. Aging pathobiology and therapeutics, 4(3), 76-83. PMID: 36250163 PMCID: PMC9562127 DOI: 10.31491/apt.2022.09.089</ref>

	In animal models of myocardial infarction and ischemia–reperfusion injury elamipretide yielded promising results, showing reduced infarct size and improved left ventricular (LV) contractile function,<ref>Dai, W., Shi, J., Gupta, R. C., Sabbah, H. N., Hale, S. L., & Kloner, R. A. (2014). Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats. Journal of cardiovascular pharmacology, 64(6), 543-553. PMID: 25165999 DOI: 10.1097/FJC.0000000000000155</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref><ref>Werbner, B., Tavakoli-Rouzbehani, O. M., Fatahian, A. N., & Boudina, S. (2023). The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure. The journal of cardiovascular aging, 3(1). PMID: 36742465 PMCID: PMC9894375 DOI: 10.20517/jca.2022.42</ref><ref>Brown, D. A., Hale, S. L., Baines, C. P., Rio, C. L. D., Hamlin, R. L., Yueyama, Y., ... & Kloner, R. A. (2014). Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. Journal of cardiovascular pharmacology and therapeutics, 19(1), 121-132. PMID: 24288396 PMCID: PMC4103197 DOI: 10.1177/1074248413508003</ref> in particular by suppressing cardiac fibrosis in the border zone of the infarcted heart,<ref>Shi, J., Dai, W., Hale, S. L., Brown, D. A., Wang, M., Han, X., & Kloner, R. A. (2015). Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart. Life sciences, 141, 170-178. PMID: 26431885 PMCID: PMC4973309 DOI: 10.1016/j.lfs.2015.09.022</ref>		In animal models of myocardial infarction and ischemia–reperfusion injury elamipretide yielded promising results, showing reduced infarct size and improved left ventricular (LV) contractile function,<ref>Dai, W., Shi, J., Gupta, R. C., Sabbah, H. N., Hale, S. L., & Kloner, R. A. (2014). Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats. Journal of cardiovascular pharmacology, 64(6), 543-553. PMID: 25165999 DOI: 10.1097/FJC.0000000000000155</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref><ref>Werbner, B., Tavakoli-Rouzbehani, O. M., Fatahian, A. N., & Boudina, S. (2023). The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure. The journal of cardiovascular aging, 3(1). PMID: 36742465 PMCID: PMC9894375 DOI: 10.20517/jca.2022.42</ref><ref>Brown, D. A., Hale, S. L., Baines, C. P., Rio, C. L. D., Hamlin, R. L., Yueyama, Y., ... & Kloner, R. A. (2014). Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. Journal of cardiovascular pharmacology and therapeutics, 19(1), 121-132. PMID: 24288396 PMCID: PMC4103197 DOI: 10.1177/1074248413508003</ref> in particular by suppressing cardiac fibrosis in the border zone of the infarcted heart,<ref>Shi, J., Dai, W., Hale, S. L., Brown, D. A., Wang, M., Han, X., & Kloner, R. A. (2015). Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart. Life sciences, 141, 170-178. PMID: 26431885 PMCID: PMC4973309 DOI: 10.1016/j.lfs.2015.09.022</ref>

Dmitry Dzhagarov at 20:37, 28 March 2023

2023-03-28T20:37:27Z

← Older revision		Revision as of 20:37, 28 March 2023
Line 9:		Line 9:
	However, elamipretide has failed to show promising results in clinical trials in patients with various heart failure phenotypes ([https://www.clinicaltrials.gov/ct2/history/NCT02814097 NCT02814097], [https://www.clinicaltrials.gov/ct2/history/NCT02914665 NCT02914665], [https://www.clinicaltrials.gov/ct2/history/NCT02788747 NCT02788747]).		However, elamipretide has failed to show promising results in clinical trials in patients with various heart failure phenotypes ([https://www.clinicaltrials.gov/ct2/history/NCT02814097 NCT02814097], [https://www.clinicaltrials.gov/ct2/history/NCT02914665 NCT02914665], [https://www.clinicaltrials.gov/ct2/history/NCT02788747 NCT02788747]).

	Elamipretide has also improved mitochondrial function in kidneys in large animal studies.		Elamipretide has also improved mitochondrial function in kidneys in large animal studies.<ref>Zhu, Y., Luo, M., Bai, X., Li, J., Nie, P., Li, B., & Luo, P. (2022). SS-31, a mitochondria-targeting peptide, ameliorates kidney disease. Oxidative Medicine and Cellular Longevity, 2022. PMID: 35707274 PMCID: PMC9192202 DOI: 10.1155/2022/1295509</ref>

	== References ==		== References ==

Dmitry Dzhagarov at 20:08, 28 March 2023

2023-03-28T20:08:30Z

← Older revision		Revision as of 20:08, 28 March 2023
Line 1:		Line 1:
	'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.<ref>Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136 DOI: 10.1007/s11095-011-0476-8</ref> SS-31 binds selectively to cardiolipin that prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron carrying function. As a result, SS-31 protects the structure of mitochondrial cristae and promotes oxidative phosphorylation. SS-31 represents a class of compounds that can recharge the cellular powerhouse and restore bioenergetics.<ref>Szeto, H. H. (2014). First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British journal of pharmacology, 171(8), 2029-2050. PMID: 24117165 PMCID: PMC3976620 DOI: 10.1111/bph.12461</ref>		'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small cell-permeable tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.<ref>Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136 DOI: 10.1007/s11095-011-0476-8</ref> SS-31 binds selectively to cardiolipin that prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron carrying function. This optimizes mitochondrial electron transport and ATP synthesis and prevents ROS production at the electron transport chain.<ref>Birk, A. V., Chao, W. M., Bracken, C., Warren, J. D., & Szeto, H. H. (2014). Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. British journal of pharmacology, 171(8), 2017-2028. PMID: 24134698 PMCID: PMC3976619 DOI: 10.1111/bph.12468</ref> As a result, SS-31 protects the structure of mitochondrial cristae and promotes oxidative phosphorylation. SS-31 represents a class of compounds that can recharge the cellular powerhouse and restore bioenergetics.<ref>Szeto, H. H. (2014). First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British journal of pharmacology, 171(8), 2029-2050. PMID: 24117165 PMCID: PMC3976620 DOI: 10.1111/bph.12461</ref>

	Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>		Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>
			.Treatment with SS-31 SS-31 reversed age-related decline in maximum mitochondrial ATP production (ATPmax) and coupling of oxidative phosphorylation (P/O); restores redox homeostasis, improves mitochondrial quality, and increases exercise tolerance in aged mice without an increase in mitochondrial content.<ref>Campbell, M. D., Duan, J., Samuelson, A. T., Gaffrey, M. J., Merrihew, G. E., Egertson, J. D., ... & Marcinek, D. J. (2019). Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radical Biology and Medicine, 134, 268-281. PMID: 30597195 PMCID: PMC6588449 DOI: 10.1016/j.freeradbiomed.2018.12.031</ref><ref>Siegel, M. P., Kruse, S. E., Percival, J. M., Goh, J., White, C. C., Hopkins, H. C., ... & Marcinek, D. J. (2013). Mitochondrial‐targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging cell, 12(5), 763-771.
			PMID: 23692570 PMCID: PMC3772966 DOI: 10.1111/acel.12102</ref><ref>Campbell, M. D., Samuelson, A. T., Chiao, Y. A., Sweetwyne, M. T., Ladiges, W. C., Rabinovitch, P. S., & Marcinek, D. J. (2023). Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice. GeroScience, 1-11. PMID: 36840897 DOI: 10.1007/s11357-023-00754-0</ref>

			In animal models of myocardial infarction and ischemia–reperfusion injury elamipretide yielded promising results, showing reduced infarct size and improved left ventricular (LV) contractile function,<ref>Dai, W., Shi, J., Gupta, R. C., Sabbah, H. N., Hale, S. L., & Kloner, R. A. (2014). Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats. Journal of cardiovascular pharmacology, 64(6), 543-553. PMID: 25165999 DOI: 10.1097/FJC.0000000000000155</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref><ref>Werbner, B., Tavakoli-Rouzbehani, O. M., Fatahian, A. N., & Boudina, S. (2023). The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure. The journal of cardiovascular aging, 3(1). PMID: 36742465 PMCID: PMC9894375 DOI: 10.20517/jca.2022.42</ref><ref>Brown, D. A., Hale, S. L., Baines, C. P., Rio, C. L. D., Hamlin, R. L., Yueyama, Y., ... & Kloner, R. A. (2014). Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. Journal of cardiovascular pharmacology and therapeutics, 19(1), 121-132. PMID: 24288396 PMCID: PMC4103197 DOI: 10.1177/1074248413508003</ref> in particular by suppressing cardiac fibrosis in the border zone of the infarcted heart,<ref>Shi, J., Dai, W., Hale, S. L., Brown, D. A., Wang, M., Han, X., & Kloner, R. A. (2015). Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart. Life sciences, 141, 170-178. PMID: 26431885 PMCID: PMC4973309 DOI: 10.1016/j.lfs.2015.09.022</ref>

			However, elamipretide has failed to show promising results in clinical trials in patients with various heart failure phenotypes ([https://www.clinicaltrials.gov/ct2/history/NCT02814097 NCT02814097], [https://www.clinicaltrials.gov/ct2/history/NCT02914665 NCT02914665], [https://www.clinicaltrials.gov/ct2/history/NCT02788747 NCT02788747]).

			Elamipretide has also improved mitochondrial function in kidneys in large animal studies.

	== References ==		== References ==

Dmitry Dzhagarov: Created page with "'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136..."

2023-03-28T17:35:22Z

Created page with "'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.<ref>Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136..."

New page

'''Elamipretide''' also known as '''SS-31''' (Szeto-Schiller 31), '''MTP-131''' and '''Bendavia''' is a small tetrapeptide ('''D-Arg-dimethylTyr-Lys-Phe-NH2''') which is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane.<ref>Szeto, H. H., & Schiller, P. W. (2011). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical research, 28, 2669-2679. PMID: 21638136 DOI: 10.1007/s11095-011-0476-8</ref> SS-31 binds selectively to cardiolipin that prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron carrying function. As a result, SS-31 protects the structure of mitochondrial cristae and promotes oxidative phosphorylation. SS-31 represents a class of compounds that can recharge the cellular powerhouse and restore bioenergetics.<ref>Szeto, H. H. (2014). First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British journal of pharmacology, 171(8), 2029-2050. PMID: 24117165 PMCID: PMC3976620 DOI: 10.1111/bph.12461</ref>

Elamipretide is a pharmacologic agent the effect of which on mitochondria makes it possible to improve physiological parameters in mitochondrial myopathies and in aging.<ref name="Two">Whitson, J. A., Bitto, A., Zhang, H., Sweetwyne, M. T., Coig, R., Bhayana, S., ... & Rabinovitch, P. S. (2020). SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell, 19(10), e13213. PMID: 32779818 PMCID: PMC7576234 DOI: 10.1111/acel.13213</ref><ref>Sabbah, H. N., Gupta, R. C., Kohli, S., Wang, M., Hachem, S., & Zhang, K. (2016). Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure, 9(2), e002206. PMID: 26839394 PMCID: PMC4743543 DOI: 10.1161/CIRCHEARTFAILURE.115.002206</ref>

== References ==
<references />
[[Category:Main list]]
[[Category:Drafts]]
[[Category:Drugs]]