Elampretide (SS-31)

Elampretide, also known as SS-31, is a synthetic tetrapeptide that reduces the production of harmful reactive oxygen species in the body. It works by targeting the cell’s powerhouse known as mitochondria which in turn restores various important cellular processes. Studies show that SS-31 has anti-aging effects that are beneficial for the treatment of age-related diseases, genetic disorders, impaired blood circulation, kidney injury, and heart disease.

Overall Health Benefits

• Lowers risk of heart disease [1-16]
• Prevents cancer [17-20]
• Boosts brain power [21-24]
• Prevents kidney injury [25-27]
• Treats lung injury [28-29]

Proven Health Benefits

Lowers Risk of Heart Disease

Studies show that SS-31 can help protect against heart disease:

• A study showed that SS-31 improved mitochondrial function in failing human heart. [1]
• In aged mouse hearts, SS-31 significantly improved mitochondrial function. [2]
• A study showed that SS-31 treatment can help protect against cardiovascular disease by reducing reactive oxygen species levels. [3]
• In patients with dilated cardiomyopathy, researchers found that SS-31 could be a potential therapy. [4]
• A study showed that SS-31 can help re-energize the mitochondria of heart cells. [5]
• In one study, SS-31 therapy protected against heart damage caused by blood vessel constriction. [6]
• A study showed that SS-31 can effectively protect the heart from infection-induced heart damage by inhibiting oxidative stress and inflammation. [7]
• A study reported that SS-31 ameliorated cardiomyopathy, a condition that affects the pumping ability of the heart. [8]
• In rats suffering from cardiac arrest, SS-31 treatment increased survival time. [9]
• A study showed that SS-31’s effect on the cell’s mitochondria can be considered as a therapeutic strategy for treating heart failure. [10]
• A study showed that long term SS-31 therapy normalized the critical abnormalities of the mitochondria. [11]
• In patients with heart enlargement and weakening, 12 weeks of SS-31 treatment improved heart function. [12]
• In patients with narrowing of the heart arteries, SS-31 treatment resulted in improvement of symptoms. [13]
• In patients with heart disease, treatment with SS-31 increased exercise tolerance. [14]
• A study showed that SS-31 can effectively treat heart disease caused by poor blood circulation. [15]
• A study also found that SS-31 can treat heart disease caused by low oxygen levels. [16]

Prevents Cancer

Evidence also found that SS-31 has anti-cancer properties:

• In mice, SS-31 prevented mitochondrial dysfunction which in turn reduced cancer prevalence. [17]
• Studies also suggest that restoring the function of the cell’s mitochondria, which is the primary action of SS-31, can help prevent cancer. [18-20]

Boosts Brain Power

SS-31 has also been found to improve cognitive function:

• In mice with cognitive deficit, SS-31 treatment rescued learning and memory deficits. [21]
• A study showed that SS-31 protected against isofluran-induced cognitive deficits. [22]
• In aged mice, treatment with SS-31 improved working memory, motor skill learning, and gait coordination. [23]
• A study showed that SS-31 has therapeutic potential in preventing damage from oxidative stress and brain cell inflammation. [24]

Prevents Kidney Injury

Studies also show that SS-31 is essential for kidney health:

• In mice with acute kidney injury, SS-31 treatment effectively suppressed mitochondrial reactive oxygen species which can contribute to further kidney damage. [25]
• A study showed that SS-31 was able to increase the production of angiotensin AT2 receptor (AT2R) which in turn reduced kidney damage. [26]
• A study showed that SS-31 significantly attenuated the effects of obstruction on all aspects of kidney damage. [27]

Treats Lung Injury

SS-31 has also been found to treat various forms of lung injury:

• In a mouse model, SS-31 attenuated mitochondrial dysfunction, reduced inflammatory responses and alleviated the severity of lung damage. [28]
• In mice, SS-31 protected against spinal cord injury-induced lung injury. [29]

References:

1. Chatfield KC, Sparagna GC, Chau S, et al. Elamipretide Improves Mitochondrial Function in the Failing Human Heart. JACC Basic Transl Sci. 2019;4(2):147-157. Published 2019 Apr 29. doi:10.1016/j.jacbts.2018.12.005.
2. Available from https://www.pnas.org/content/117/26/15363.
3. Escribano-Lopez, I., Diaz-Morales, N., Iannantuoni, F. et al. The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes. Sci Rep 8, 15862 (2018). https://doi.org/10.1038/s41598-018-34251-8.
4. Machiraju P, Wang X, Sabouny R, Huang J, Zhao T, Iqbal F, King M, Prasher D, Lodha A, Jimenez-Tellez N, Ravandi A, Argiropoulos B, Sinasac D, Khan A, Shutt TE and Greenway SC (2019) SS-31 Peptide Reverses the Mitochondrial Fragmentation Present in Fibroblasts From Patients With DCMA, a Mitochondrial Cardiomyopathy. Front. Cardiovasc. Med. 6:167. doi: 10.3389/fcvm.2019.00167.
5. Available from https://jasn.asnjournals.org/content/24/8/1250.
6. Lu HI, Lee FY, Wallace CG, et al. SS31 therapy effectively protects the heart against transverse aortic constriction-induced hypertrophic cardiomyopathy damage. Am J Transl Res. 2017;9(12):5220-5237. Published 2017 Dec 15.
7. Liu Y, Yang W, Sun X, Xie L, Yang Y, Sang M, Jiao R. SS31 Ameliorates Sepsis-Induced Heart Injury by Inhibiting Oxidative Stress and Inflammation. Inflammation. 2019 Dec;42(6):2170-2180. doi: 10.1007/s10753-019-01081-3. PMID: 31494795.
8. Dai DF, Chen T, Szeto H, et al. Mitochondrial targeted antioxidant Peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol. 2011;58(1):73-82. doi:10.1016/j.jacc.2010.12.044.
9. Zhang W, Tam J, Shinozaki K, Yin T, Lampe JW, Becker LB, Kim J. Increased Survival Time With SS-31 After Prolonged Cardiac Arrest in Rats. Heart Lung Circ. 2019 Mar;28(3):505-508. doi: 10.1016/j.hlc.2018.01.008. Epub 2018 Feb 7. PMID: 29503242; PMCID: PMC6081272.
10. Chavez JD, Tang X, Campbell MD, Reyes G, Kramer PA, Stuppard R, Keller A, Zhang H, Rabinovitch PS, Marcinek DJ, Bruce JE. Mitochondrial protein interaction landscape of SS-31. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15363-15373. doi: 10.1073/pnas.2002250117. Epub 2020 Jun 17. PMID: 32554501; PMCID: PMC7334473.
11. Sabbah, H.N., Gupta, R.C., Singh-Gupta, V. et al. Abnormalities of Mitochondrial Dynamics in the Failing Heart: Normalization Following Long-Term Therapy with Elamipretide. Cardiovasc Drugs Ther 32, 319–328 (2018). https://doi.org/10.1007/s10557-018-6805-y.
12. Available from https://www.medrxiv.org/content/10.1101/2020.11.20.20235580v2.full.
13. Available from https://www.ahajournals.org/doi/full/10.1161/circinterventions.117.005487.
14. Available from https://europepmc.org/articles/pmc6588449/bin/nihms1005643-supplement-supplemental_material.pdf.
15. Szeto HH, Liu S, Soong Y, et al. Mitochondria Protection after Acute Ischemia Prevents Prolonged Upregulation of IL-1β and IL-18 and Arrests CKD. J Am Soc Nephrol. 2017;28(5):1437-1449. doi:10.1681/ASN.2016070761.
16. Saad A, Herrmann SMS, Eirin A, et al. Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis. Circ Cardiovasc Interv. 2017;10(9):e005487. doi:10.1161/CIRCINTERVENTIONS.117.005487.
17. Smuder AJ, Roberts BM, Wiggs MP, Kwon OS, Yoo JK, Christou DD, Fuller DD, Szeto HH, Judge AR. Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness. Oncotarget. 2020 Sep 22;11(38):3502-3514. doi: 10.18632/oncotarget.27748. PMID: 33014286; PMCID: PMC7517961.
18. Wang B, Fu J, Yu T, Xu A, Qin W, Yang Z, Chen Y, Wang H. Contradictory effects of mitochondria- and non-mitochondria-targeted antioxidants on hepatocarcinogenesis by altering DNA repair in mice. Hepatology. 2018 Feb;67(2):623-635. doi: 10.1002/hep.29518. Epub 2018 Jan 7. PMID: 28898446.
19. Chavez JD, Tang X, Campbell MD, Reyes G, Kramer PA, Stuppard R, Keller A, Zhang H, Rabinovitch PS, Marcinek DJ, Bruce JE. Mitochondrial protein interaction landscape of SS-31. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15363-15373. doi: 10.1073/pnas.2002250117. Epub 2020 Jun 17. PMID: 32554501; PMCID: PMC7334473.
20. Ma W, Zhu X, Ding X, et al. Protective effects of SS31 on t‑BHP induced oxidative damage in 661W cells. Mol Med Rep. 2015;12(4):5026-5034. doi:10.3892/mmr.2015.4055.
21. Jia YL, Sun SJ, Chen JH, Jia Q, Huo TT, Chu LF, Bai JT, Yu YJ, Yan XX, Wang JH. SS31, a Small Molecule Antioxidant Peptide, Attenuates β-Amyloid Elevation, Mitochondrial/Synaptic Deterioration and Cognitive Deficit in SAMP8 Mice. Curr Alzheimer Res. 2016;13(3):297-306. doi: 10.2174/1567205013666151218150004. PMID: 26679857.
22. Wu J, Hao S, Sun XR, et al. Elamipretide (SS-31) Ameliorates Isoflurane-Induced Long-Term Impairments of Mitochondrial Morphogenesis and Cognition in Developing Rats. Front Cell Neurosci. 2017;11:119. Published 2017 Apr 25. doi:10.3389/fncel.2017.00119.
23. Tarantini, S, Valcarcel‐Ares, NM, Yabluchanskiy, A, et al. Treatment with the mitochondrial‐targeted antioxidant peptide SS‐31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice. Aging Cell. 2018; 17:e12731. https://doi.org/10.1111/acel.12731.
24. Zhao, W., Xu, Z., Cao, J. et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice. J Neuroinflammation 16, 230 (2019). https://doi.org/10.1186/s12974-019-1627-9.
25. Available from https://www.sciencedirect.com/science/article/pii/S0753332220307149.
26. Wyss J-C, Kumar R, Mikulic J, Schneider M, Mary J-L, Aebi JD, Juillerat-Jeanneret L and Golshayan D (2019) Differential Effects of the Mitochondria-Active Tetrapeptide SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2) and Its Peptidase-Targeted Prodrugs in Experimental Acute Kidney Injury. Front. Pharmacol. 10:1209. doi: 10.3389/fphar.2019.01209.
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29. Zhu LL, Li MQ, He F, Zhou SB, Jiang W. Mitochondria Targeted Peptide Attenuates Mitochondrial Dysfunction, Controls Inflammation and Protects Against Spinal Cord Injury-Induced Lung Injury. Cell Physiol Biochem. 2017;44(1):388-400. doi: 10.1159/000484919. Epub 2017 Nov 13. PMID: 29132140.