Elampretide (SS-31)

Overall Health Benefits of Elampretide

• Improves cardiovascular health [1-29]
• Boosts brain power [30-42]
• Prevents cancer [43-48]
• Prevents kidney injury [49-63]
• Treats lung injury [64-66]

What is Elampretide?

Elampretide, also known as elamipretide or 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.

How Elampretide Works?

The mitochondria are known as the “powerhouse of the cell” as they produce the energy required for various cellular processes. Dysfunctional mitochondria can lead to a wide array of inherited mitochondrial diseases and some age-related diseases. In addition, dysfunctional mitochondria produce abnormally high levels of oxidative factors that can significantly damage cardiolipin, a lipid that plays an integral role in the maintenance of the structural integrity of the mitochondria. By binding to cardiolipin, elampretide protects it from the harmful effects of oxidative stress. This in turn prevents or reduces mitochondrial membrane dysfunction and cell death. In addition, the protective effects of elampretide on the mitochondria help restore various important cellular processes.

Chemical Structure of Elampretide

Research on Elampretide

Improves Cardiovascular Health

Studies show that elampretide (SS-31) can help protect against heart disease via different mechanisms:

1. In the failing human heart, SS-31 improved mitochondrial function. [1]
2. In aged mouse hearts, SS-31 significantly improved mitochondrial function. [2]
3. In patients with type 2 diabetes, SS-31 treatment protected against cardiovascular disease by reducing reactive oxygen species levels. [3]
4. In patients with dilated cardiomyopathy, SS-31 reversed the mitochondrial fragmentation. [4]
5. A study showed that SS-31 can help re-energize the mitochondria of heart cells. [5]
6. In adult-male mice, SS-31 therapy protected against heart damage caused by blood vessel constriction. [6]
7. In mice exposed to systemic inflammation, SS-31 effectively protected the heart from infection-induced heart damage by inhibiting oxidative stress and inflammation. [7]
8. In mice with heart failure, SS-31 ameliorated cardiomyopathy, a condition that affects the pumping ability of the heart. [8]
9. In rats suffering from cardiac arrest, SS-31 treatment increased survival time. [9]
10. A study showed that SS-31’s effect on the cell’s mitochondria can be considered a therapeutic strategy for treating heart failure. [10]
11. In healthy dogs and healthy donor human hearts, long-term SS-31 therapy normalized the critical abnormalities of the mitochondria. [11]
12. In patients with heart enlargement and weakening, 12 weeks of SS-31 treatment improved heart function. [12]
13. In patients with narrowing of the heart arteries, SS-31 treatment resulted in improvement of the symptoms. [13]
14. In patients with heart disease, treatment with SS-31 increased exercise tolerance. [14]
15. In rats, SS-31 administration for 6 weeks effectively treated heart disease caused by poor blood circulation. [15]
16. In mouse hearts, SS-31 treatment for 8 weeks significantly reduced the levels of oxidative stress. [16]
17. In cells derived from children with dilated cardiomyopathy with ataxia syndrome (DCMA), the abnormalities in the mitochondria were reversed by incubation with SS-31 for 24 hours. [17]
18. In old mice that received SS-31 for 8 weeks, significant improvements in skeletal muscle function and endurance, cardiac function, and exercise endurance were observed. [18]
19. In mice with cancer receiving SS-31 in both the heart and diaphragm muscle, a significant improvement in cardiorespiratory function was observed. [19]
20. In old mice and rats, SS-31 reversed cardiac dysfunction by reducing excessive proton leak. [20-21]
21. In old mouse hearts, SS-31 was effective at restoring different aspects of mitochondrial and heart health via reduction of oxidative stress. [22-24]
22. In dogs with advanced heart failure, elamipretide improved left ventricular and mitochondrial function. [25-26]
23. In rats with insufficient blood flow to the heart, elamipretide mitigated impairments in mitochondrial structure-function. [27]
24. In patients with Barth syndrome (characterized by enlarged heart, muscle weakness, fatigue, and low blood cell count), elamipretide improved knee extensor strength, patient global impression of symptoms, and some cardiac parameters. [28]
25. In aged mice, SS-31 reversed age-related redox stress and improved exercise tolerance. [29]

Boosts Brain Power

SS-31 has also been found to improve cognitive function through its ability to protect the neurons (nerve cells) in the brain:

1. In mice with cognitive deficits, SS-31 treatment rescued learning and memory deficits. [30]
2. In developing rat brains, SS-31 protected against isoflurane-induced cognitive deficits through the reversal of mitochondrial dysfunction and regulation of BDNF (brain-derived neurotrophic factor) signaling. [31-32]
3. In aged mice, treatment with SS-31 improved working memory, motor skill learning, and gait coordination. [33]
4. A study showed that SS-31 has therapeutic potential in preventing damage from oxidative stress and brain cell inflammation. [34]
5. In aged mice, treatment with elamipretide significantly enhanced working memory and motor skill learning by increasing the blood flow to the brain. [35]
6. In aged mice, SS-31 treatment was associated with significant improvements in learning and spatial working memory and lower levels of inflammatory cytokines. [36]
7. Treatment of aged mice with the mitochondrial-targeted peptide elamipretide protected against mitochondrial dysfunction and attenuated surgery-induced cognitive deficits. [37]
8. In hypertensive rats with traumatic brain injury, SS-31 treatment reversed cerebrovascular oxidative stress which is linked to dysregulation of blood flow to the brain and cognitive dysfunction. [38]
9. In animal models of Parkinson’s disease (PD), SS-31 exerted neuroprotective effects on dopamine neurons (play a role in memory, movement, motivation, mood, and attention) by targeting both mitochondrial dysfunction and oxidative damage. [39]
10. In a model of Alzheimer’s disease, SS-31 protected the brain cells against programmed cell death (apoptosis) and significantly reduced mitochondrial dysfunction. [40]
11. In murine cultured microglial cells (nervous system cells), SS-31 protected the cells against lipopolysaccharide (LPS)-induced inflammation and oxidative stress by stabilizing the mitochondrial structure. [41-42]

Prevents Cancer

Evidence also found that SS-31’s antioxidant properties and ability to protect the mitochondria from damage may play a role in preventing cancer:

1. In mice, SS-31 prevented mitochondrial dysfunction which in turn reduced cancer prevalence. [43]
2. Studies also suggest that restoring the function of the cell’s mitochondria, which is the primary action of SS-31, can help prevent cancer. [44-46]
3. In cancer patients, SS-31 prevented cancer cachexia (muscle wasting) and improved systemic energy homeostasis. [48]

Prevents Kidney Injury

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

1. In mice with acute kidney injury, SS-31 treatment effectively suppressed mitochondrial reactive oxygen species which can contribute to further kidney damage. [49]
2. In murine models of kidney injury, SS-31 was able to increase the production of angiotensin AT2 receptor (AT2R) which in turn reduced kidney damage. [50]
3. In rats with unilateral ureteral obstruction, SS-31 significantly attenuated the effects of obstruction on all aspects of kidney damage. [51-52]
4. In patients with severe atherosclerotic renal artery stenosis (narrowing of the kidney arteries due to blockage), intravenous infusion of elamipretide at 0.05 mg/kg per hour increased blood flow to the kidney and improved kidney function compared with placebo treatment. [53]
5. In mice with diabetes, elamipretide protected against the progression of diabetic kidney disease. [54]
6. In animal and cell models, SS-31 ameliorated kidney disease by preventing programmed cell death, inflammation, and scarring. [55]
7. In pregnant mice, elamipretide was found to ameliorate the progression of kidney disease without any adverse effects. [56]
8. In mice models of chronic kidney disease (CKD), SS-31 preserved mitochondrial integrity, ameliorated the increase in the levels of all inflammatory markers, restored glomerular filtration rate (filtering ability of the kidneys), and prevented kidney scarring. [57-58]
9. In mice of advanced age, SS-31 improved glomerular filtration rate and mitochondrial structure. [59]
10. In murine models of acute tubular injury and glomerular damage, SS-31 reduced damage to the kidneys by increasing the levels of the antibody known as AT₂ [60]
11. In swine with atherosclerotic renal artery stenosis, treatment with subcutaneous elamipretide (5d/wk) for 4 weeks improved kidney function and alleviated fibrosis (scarring) and oxidative stress. [61]
12. In mice fed with a high-fat diet, SS-31 prevented the loss of kidney cells and lipid accumulation. [62]
13. In rats with insufficient blood flow to the kidneys (ischemia), SS-31 prevented mitochondrial swelling and protected against scarring and loss of blood vessels. [63]

Treats Lung Injury

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

1. In a mouse model, SS-31 attenuated mitochondrial dysfunction, reduced inflammatory responses, and alleviated the severity of lung damage. [64]
2. In mice, SS-31 protected against spinal cord injury-induced lung injury. [65]
3. In mice with acute liver injury due to blood infection (sepsis), the mitochondria-targeted antioxidant SS-31 reduced oxidative stress and inflammatory markers and alleviated sepsis-related acute liver injury. [66]

Associated Side Effects of Elampretide

Elampretide side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on elampretide. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of elampretide. Despite this, it was listed as a side effect associated with elampretide even though these associated side effects are very uncommon.
Side effects associated with elampretide may include the following:

• Abdominal pain
• Dizziness
• Flatulence
• Headache

References

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