Elamipretide: How the SS-31 Peptide Became an Approved Medicine

On 19 September 2025, the US Food and Drug Administration granted accelerated approval to a medicine that had begun life as a laboratory curiosity: a four-amino-acid peptide that seeks out the inner membrane of the mitochondria. The medicine was elamipretide, the clinical name of the research peptide SS-31, and it became the first approved treatment for Barth syndrome, a rare inherited disease that starves the body’s cells of energy. It was a milestone not only for patients with a devastating condition, but for the whole field of mitochondrial medicine.

This guide tells the elamipretide story: where it came from, how it works, what the key clinical trials found, including those that did not succeed, why its approval matters, and how the clinical medicine relates to the SS-31 research peptide used in laboratories. It is an educational overview of research and regulatory history, not medical advice. Crown Peptides supplies SS-31 for laboratory research use only; it is not the licensed medicine.

The Short Answer

Elamipretide is the clinical name for SS-31, a small peptide that concentrates on the inner mitochondrial membrane, where it binds cardiolipin, a lipid essential for the machinery that produces cellular energy. It was developed from research by Hazel Szeto and Peter Schiller and taken into clinical trials by Stealth BioTherapeutics. After a long and uneven clinical programme, including trials that did not meet their goals, it received accelerated US approval in September 2025 for Barth syndrome, based on improvements in muscle strength.

One Molecule, Several Names

The same peptide has appeared under several different names over its long history, which can be genuinely confusing for anyone reading about it. SS-31 is its original laboratory name, from the Szeto-Schiller series of peptides. MTP-131 and Bendavia were earlier development names. Elamipretide is its international nonproprietary name, the official generic name used in clinical research and on the approved medicine. They all refer to the same four-building-block sequence: D-arginine, dimethyltyrosine, lysine and phenylalanine, with an amidated end.

Mitochondria in Plain English

Mitochondria are tiny structures inside almost every cell, often called the cell’s power stations. They take the fuel from food, sugars and fats, and use oxygen to turn it into ATP, the molecule cells use as energy. A single cell can contain hundreds or thousands of them, and tissues that use the most energy, such as heart muscle, skeletal muscle and the brain, have the most. When mitochondria fail, those tissues suffer first, which is why mitochondrial diseases so often affect the heart, muscles and nervous system.

A by-product problem

Energy production has a downside. As electrons pass along the chain of protein complexes in the inner membrane, a small fraction leak out and react with oxygen, forming reactive oxygen species that can damage lipids, proteins and DNA. Damaged mitochondria tend to leak more, which can create a vicious circle of damage. Reducing that leakage is one of the main goals of mitochondrial research, and one of the proposed effects of SS-31.

Where It Came From

The Szeto-Schiller peptides

In the late 1990s and early 2000s, Hazel Szeto at Weill Cornell Medical College and Peter Schiller at the Clinical Research Institute of Montreal were designing small peptides for pain research when they noticed something unexpected: some of them concentrated inside mitochondria. That was unusual, because most molecules, especially charged ones, cannot easily cross the membranes that surround mitochondria. The team developed a series of such peptides and numbered them. SS-31 became the lead compound.

A different target

Rather than being a pain medicine, SS-31 turned out to protect mitochondria. A 2014 review in the British Journal of Pharmacology by Szeto described it as a first-in-class cardiolipin-protective compound able to restore mitochondrial energy production in many disease models (PMID: 24117165, PMC3976620). The review explained how SS-31 selectively targets cardiolipin on the inner mitochondrial membrane, protecting the structure of the energy machinery and reducing the leakage of harmful reactive oxygen species.

How It Works

The inner mitochondrial membrane

Mitochondria have two membranes. The inner one is folded into ridges called cristae, packed with the protein complexes that turn fuel into ATP, the cell’s energy currency. The shape of the cristae and the arrangement of those complexes are essential for efficient energy production.

Cardiolipin

Cardiolipin is a lipid found almost only in the inner mitochondrial membrane. It helps hold the energy-producing complexes together in efficient groupings and helps shape the cristae. When cardiolipin is damaged or abnormal, energy production falters and more reactive oxygen species leak out.

What SS-31 does

SS-31 carries positive charges and aromatic rings that allow it to cross membranes and bind cardiolipin. Research indicates that by binding cardiolipin, it helps stabilise the inner membrane, preserves cristae structure and supports efficient electron transport, reducing reactive oxygen species. Our article SS-31 peptide guide covers its laboratory research in depth.

Barth Syndrome: The Disease It Was Approved For

A cardiolipin disease

Barth syndrome is a rare inherited condition, affecting almost only males, caused by mutations in the TAZ gene, which encodes tafazzin, an enzyme that remodels cardiolipin into its mature form. Without working tafazzin, cardiolipin is abnormal, mitochondria function poorly and the body’s most energy-hungry tissues suffer. Patients typically have heart muscle disease, muscle weakness, severe fatigue, low levels of a type of white blood cell and growth delay.

Why SS-31 was a natural candidate

Because Barth syndrome is fundamentally a disease of cardiolipin, a peptide that binds and stabilises cardiolipin was a logical candidate. Barth syndrome also had no approved treatment, making the need urgent.

A Short History of Barth Syndrome

Barth syndrome is named after Peter Barth, a Dutch paediatric neurologist who described a family with the condition in 1983, noting a combination of heart muscle disease, muscle weakness and low white blood cell counts in boys across several generations. In the 1990s, researchers traced it to the TAZ gene on the X chromosome, which explains why it almost only affects males. Later work showed that tafazzin remodels cardiolipin, making Barth syndrome one of the clearest examples of a disease caused directly by abnormal cardiolipin. For decades, patients and families had only supportive care. The Barth Syndrome Foundation and affected families played a major part in supporting research and clinical trials, which is part of why a treatment was eventually developed for such a rare condition.

Why Mitochondrial Diseases Are So Hard to Treat

Mitochondrial diseases are notoriously difficult to treat. They are rare and highly varied, caused by mutations in hundreds of different genes, so trials struggle to recruit enough patients with the same condition. Symptoms fluctuate, making changes hard to measure. Standard outcome measures, such as walking distance, may not capture what matters most to patients. And many compounds that help mitochondria in the laboratory do not reach the right tissues in people. Against that background, elamipretide’s approval, even an accelerated one, was a significant achievement, and its mixed trial record is typical of the field rather than unusual.

The Clinical Trials

TAZPOWER

The key Barth syndrome trial was TAZPOWER. Its randomised, placebo-controlled phase did not meet its primary goals, but patients continued into an open-label extension in which all received elamipretide. In 2024, results after 168 weeks of that extension were published in Genetics in Medicine (PMID: 38602181). Ten patients entered and eight reached week 168. Elamipretide was well tolerated, with injection-site reactions the most common adverse events. Walking distance on the six-minute walk test improved significantly at all time points, by a cumulative 96.1 metres at week 168; fatigue scores improved; and measures of heart function showed significant trends toward improvement. The ratio of immature to mature cardiolipin also improved, consistent with the proposed mechanism.

A natural history comparison

Because Barth syndrome is so rare, researchers also compared elamipretide-treated patients with untreated patients followed over time. A 2022 study in the Orphanet Journal of Rare Diseases reported this natural history comparison to help assess efficacy (PMID: 36056411, PMC9438322).

MMPOWER-3: a trial that did not succeed

Not every trial went well, and the setbacks are an important part of the story. In MMPOWER-3, published in Neurology in 2023, 218 adults with primary mitochondrial myopathy, a group of inherited mitochondrial muscle diseases, were randomised to elamipretide or placebo for 24 weeks (PMID: 37268435, PMC10382259). Elamipretide was well tolerated, but it did not improve the six-minute walk test or fatigue compared with placebo. A later analysis suggested that effects might differ by the specific genetic cause of disease (PMID: 39574155, PMC11583740).

Other programmes

Elamipretide has also been studied in heart conditions, including heart failure and damage after heart attack, in kidney disease and in eye disease, with mixed results. Its clinical history is a reminder that promising mechanisms and animal results do not always translate into clear benefits in people.

The Accelerated Approval

On 19 September 2025, the FDA granted accelerated approval to elamipretide for Barth syndrome, based on improvement in knee extensor muscle strength, a measure of leg strength. Accelerated approval allows a medicine for a serious condition with unmet need to be approved on the basis of an effect considered reasonably likely to predict clinical benefit, with confirmatory evidence required afterwards. It made elamipretide the first approved treatment for Barth syndrome and one of the first approved medicines to target mitochondria directly.

Why it matters

For patients with Barth syndrome, it offered the first approved option. For researchers, it provided proof that a peptide designed to act on the mitochondrial membrane could reach approval, validating a whole approach to mitochondrial disease.

What Accelerated Approval Means

Accelerated approval is a US pathway for serious conditions with unmet medical need. Instead of waiting for a trial to prove a direct clinical benefit, such as longer survival or improved daily function, a medicine can be approved based on an effect on a measure that is reasonably likely to predict that benefit, in elamipretide’s case, muscle strength. The company is then required to confirm the benefit in further studies. If confirmation fails, the approval can be withdrawn. It is a way of balancing early access for patients with no other options against the need for strong evidence.

Lessons From the Elamipretide Story

Elamipretide’s path offers several lessons for anyone following peptide research. A clear mechanism, such as cardiolipin binding, is valuable but does not guarantee success in every disease. Matching the compound to the condition where the mechanism matters most, as with Barth syndrome, a cardiolipin disease, can make the difference. Rare disease trials require creative designs, such as open-label extensions and natural history comparisons. And honest reporting of negative results, such as MMPOWER-3, is as important as reporting successes, because it tells researchers where a compound does and does not help.

What Comes Next for Elamipretide

Accelerated approval is not the end of the story. Confirmatory evidence is required to maintain the approval, and researchers continue to explore whether the medicine could help in other conditions linked to cardiolipin and mitochondrial dysfunction. The post hoc analysis of MMPOWER-3, which suggested effects might differ by genetic cause, points to a possible future in which mitochondrial treatments are matched to specific genetic subtypes rather than tested across broad groups. Research into ageing, heart and eye conditions also continues. The elamipretide story is therefore still being written, both in the clinic and in the laboratory.

Why the Approval Matters for Peptide Research

For the wider peptide field, elamipretide’s approval is significant in several ways. It shows that a very small synthetic peptide, just four building blocks long, can be developed into an approved medicine. It shows that peptides can be designed to reach targets inside cells, not just receptors on the surface. And it validates cardiolipin and the inner mitochondrial membrane as targets worth pursuing. For laboratory researchers using SS-31, it provides a clinical anchor: the research tool they use shares its sequence with a molecule that has now been through the full regulatory process for one condition.

Elamipretide vs the SS-31 Research Peptide

Elamipretide and the SS-31 research peptide share the same molecular sequence, but they are different products. The approved medicine is manufactured under Good Manufacturing Practice, tested in clinical trials and prescribed for a specific condition under medical supervision. The SS-31 research peptide is supplied for laboratory research, such as cell and animal studies of mitochondrial function, and is not a medicine. Crown Peptides supplies SS-31 in 10mg and 50mg formats; the 50mg format suits larger or longer laboratory studies, where it means fewer vials to reconstitute and a single batch across the whole study. Our article what the research-use label means explains the distinction.

What Researchers Use SS-31 to Study

Mitochondrial energy production

SS-31 is used to test how stabilising cardiolipin affects respiration, ATP production and the efficiency of the electron transport chain.

Oxidative stress

It is used to study the leakage of reactive oxygen species from damaged mitochondria and its consequences.

Ageing

Because cardiolipin damage and mitochondrial decline are features of ageing, SS-31 is widely used in ageing research, including in studies of ageing muscle and heart.

Disease models

It has been studied in animal models of heart, kidney, eye and nervous system disease.

SS-31 in Ageing Research

Beyond disease, SS-31 has become one of the most widely used tools in mitochondrial ageing research. Studies in aged mice have examined whether it can improve the energy output of ageing muscle and the function of ageing hearts, with researchers at the University of Washington among those reporting improvements in muscle energetics and exercise performance in old animals. Because cardiolipin damage and less efficient mitochondria are features of ageing tissue, SS-31 offers a way to test how much of age-related decline stems from the mitochondrial membrane itself. Our longevity research guide places it alongside other ageing research tools.

Designing SS-31 Research

Useful measures include mitochondrial respiration, measured by oxygen consumption; ATP production; reactive oxygen species; cristae structure by electron microscopy; and cardiolipin composition by mass spectrometry. Including functional measures, such as muscle strength or heart function in animal models, links mitochondrial effects to outcomes, echoing the measures used in the clinical trials.

How Trial Outcomes Were Measured

The six-minute walk test

The most common measure in the elamipretide trials was the six-minute walk test, which records how far a person can walk in six minutes. It is simple and reflects everyday function, but it can vary from day to day, and in rare diseases with small trials it can be hard to show a clear difference.

Fatigue scores

Because fatigue is one of the most disabling symptoms of mitochondrial disease, trials used standardised questionnaires to measure it, including a Barth syndrome-specific scale in TAZPOWER.

Muscle strength

Knee extensor strength, a measure of the power of the thigh muscles, was the basis of the accelerated approval.

Heart function

Because the heart is heavily affected in Barth syndrome, echocardiography measured changes in heart size and pumping.

Biomarkers

The ratio of immature to mature cardiolipin, measured in blood cells, offered a direct window onto the disease mechanism, and improved in the TAZPOWER extension.

The Wider Family of Mitochondria-Targeted Compounds

Elamipretide is one of several approaches to targeting mitochondria. Other research compounds work in different ways: MOTS-c is a peptide encoded by mitochondrial DNA that acts on the cell’s energy sensor; NAD+ supplies the coenzyme at the heart of energy metabolism; Methylene Blue can shuttle electrons within the energy chain; and antioxidants targeted to mitochondria have been developed by attaching them to positively charged carriers. What made SS-31 distinctive was its direct binding to cardiolipin and its independence from membrane potential, which set it apart from most other mitochondria-targeted molecules.

The Technical Breakdown: How a Peptide Reaches the Inner Membrane

Alternating charge and aromatic rings

SS-31’s sequence alternates positively charged residues, D-arginine and lysine, with aromatic residues, dimethyltyrosine and phenylalanine. This arrangement lets it pass through membranes despite its charge and concentrate at the inner mitochondrial membrane, which is rich in negatively charged cardiolipin.

Why it does not depend on membrane potential

Many mitochondria-targeting molecules rely on the strong negative charge across the inner membrane to pull them in, which means they work poorly in damaged mitochondria that have lost that charge. Research indicates SS-31’s uptake does not depend on membrane potential, which may help it reach precisely the damaged mitochondria that most need protection.

The D-arginine

The first amino acid is the mirror-image D form of arginine, which helps protect the peptide from breakdown by enzymes.

Dimethyltyrosine

The second residue, 2′,6′-dimethyltyrosine, is an unusual modified amino acid thought to contribute to membrane interactions and to scavenging of reactive oxygen species.

Handling SS-31 in the Laboratory

Like other research peptides, SS-31 is supplied as a freeze-dried powder and should be stored cold, dry and away from light. Once reconstituted, solutions should be kept refrigerated and used within a sensible period, and repeated freeze-thaw cycles avoided. Because studies of mitochondrial function often run over weeks and compare subtle differences, using a single batch throughout, and recording lot numbers, removes one of the most common hidden sources of variation. For longer studies, the 50mg format makes that easier. Our guides to how long peptides last and the peptide calculator cover the practical details, and Bacteriostatic Water is available alongside.

Why Quality Matters for SS-31

SS-31 contains unusual building blocks, including a D-amino acid and dimethyltyrosine, each of which must be exactly right. A version with the wrong form of an amino acid could have the same mass but different activity. Every batch supplied by Crown Peptides comes with a batch-specific certificate of analysis showing HPLC purity and mass spectrometry identity. Published certificates are on our Lab Reports page, and our guides to peptide testing and reconstitution cover the practical side.

Related Compounds and Reading

Read SS-31 vs MOTS-c, SS-31 vs NAD+ and mitochondrial peptides explained. Related compounds include MOTS-c, NAD+, Methylene Blue and L-Carnitine. Browse the ageing and cellular research peptides category.

Elamipretide Questions, Answered

What is elamipretide?

The clinical name of SS-31, a mitochondria-targeted peptide that binds cardiolipin. It was approved in the US in September 2025 for Barth syndrome.

Is elamipretide the same as SS-31?

It is the same molecular sequence. Elamipretide refers to the clinical medicine; SS-31 is the laboratory name used for the research peptide.

What is Barth syndrome, and who does it affect?

A rare inherited disease caused by mutations in the TAZ gene, which disrupt cardiolipin and mitochondrial function, causing heart and muscle problems and severe fatigue.

Did elamipretide succeed in every trial?

No. The MMPOWER-3 trial in primary mitochondrial myopathy did not meet its main goals, and results in other conditions have been mixed.

How is elamipretide different from other mitochondrial compounds?

It binds cardiolipin directly on the inner mitochondrial membrane, and research indicates its uptake does not depend on membrane potential, unlike many mitochondria-targeted molecules.

Why is cardiolipin important?

It is a lipid found almost only in the inner mitochondrial membrane, where it holds the energy-producing machinery together and shapes the cristae. Abnormal cardiolipin causes Barth syndrome.

Who developed elamipretide?

It grew from research by Hazel Szeto and Peter Schiller and was developed clinically by Stealth BioTherapeutics.

What is accelerated approval?

A US pathway that allows approval for serious conditions based on an effect reasonably likely to predict benefit, with confirmation required afterwards.

Why was SS-31 first studied in pain research?

Szeto and Schiller were originally designing small peptides for pain research when they noticed that some concentrated inside mitochondria, which redirected the work towards mitochondrial protection.

Why do mitochondrial diseases affect the heart and muscles most?

Because those tissues use the most energy and contain the most mitochondria, so they suffer first when mitochondria fail.

Is elamipretide available in the UK?

The approval described here was granted by the US FDA. Crown Peptides does not supply the medicine; it supplies the SS-31 research peptide for laboratory use.

What were the side effects in the trials?

In the TAZPOWER extension and MMPOWER-3, elamipretide was reported to be well tolerated, with injection-site reactions the most common adverse events.

What sizes does Crown Peptides supply SS-31 in?

10mg and 50mg formats, for laboratory research only.

What is its mechanism of action?

Research indicates it binds cardiolipin on the inner mitochondrial membrane, stabilising the energy-producing machinery and reducing reactive oxygen species.

From a Pain Lab to a Rare Disease Medicine

Elamipretide’s journey took more than two decades, from a surprising observation in a pain research programme to a molecule that seeks out the inner mitochondrial membrane, through years of trials that sometimes disappointed, to a landmark approval for a disease that had no treatment. It is a story of patient science, honest reporting of failures as well as successes, and a mechanism rooted in the most basic machinery of the cell, and it shows how far a well-understood research peptide can travel.

For laboratory research into mitochondrial function, explore SS-31 from Crown Peptides, every batch HPLC and mass spectrometry verified and dispatched from the UK.