The FDA-Approved Peptide for Mitochondrial Disease (What’s Next?)

The FDA approved a peptide for a rare mitochondrial disease. But what's more interesting is the more common potential use cases and expanding universe of mitochondrial medicine.

The FDA recently approved a peptide for a rare mitochondrial disease.

But that’s not the interesting part.

What is interesting is that this same molecule might have implications for some of the most common and burdensome chronic diseases on the planet, from heart disease to diabetes and even to Alzheimer’s and Parkinson’s disease.

This is certainly a peptide I might consider including in my health routine.

But not before first diving into the scientific literature. And when I did, I was struck by genuine optimism.

This is a very peculiar biomolecule that appears generally safe, with a wide variety of potential use cases. Maybe that’s not surprising since it helps shore up the foundational hub of metabolism in our bodies: the mitochondria.

Now, you might have noticed I haven’t told you what this molecule is yet.

That’s because its name sucks.

Science isn’t always great at marketing, so brace yourself.

It actually goes by many names: SS-31, elamipretide, Bendavia, MTP-131, Forzinity—even D-Arg-Dmt-Lys-Phe-NH₂.

Gosh! This molecule has more names than a Game of Thrones character.

Seriously, we could call it: “SS-31 of the Inner Membrane, First of Its Name, Binder of Cardiolipin, Keeper of the Electron Chain, Defender Against Oxidative Chaos, Restorer of Cellular Power”

But on the internet, it’s most commonly referred to as SS-31. So, that’s what we’ll call it.

Today, I’m going to tell you:

• How SS-31 works.

• How it’s being used today.

• What conditions it might soon be used to treat.

• What’s next in the universe of mitochondrial medicine.

• How I’m sourcing my peptides.

What You Need to Know About Mitochondria

I want to begin with some basic biology—the background you need to understand this.

Specifically, let’s talk about mitochondrial structure.

Mitochondria, as you probably know, generate energy for your body. But they’re also communication and signaling hubs. Physically, they look like little beans and have two membranes. The inner membrane is folded into structures called cristae—and these are absolutely critical.

I like to think of the folds in the inner mitochondrial membrane kind of like the folds in your brain… and you don’t want to be a smooth brain.

These folds increase surface area and, more important to our discussion, allow different components of the membrane to interact with each other.

And that idea of interaction is key.

For efficient energy production, you need specific components to link together. When that process breaks down, energy production fails. And when energy production fails, organ systems begin to fail.

Now, there’s a critical component here: a lipid called cardiolipin.

Cardiolipin helps give the inner membrane its structure and those elegant folds.

More specifically, it promotes the curvature of the inner mitochondrial membrane to optimize energy production through what’s known as the electron transport chain, a series of complexes (I, II, III, IV, and V) that pass electrons along to ultimately generate the energy that keeps us alive.

So that’s your biology background.

SS-31: A Mitochondrial Targeting Peptide that Stabilized Mitochondria

Now, where does SS-31 come in?

SS-31 is a peptide that uniquely localizes to the mitochondrial inner membrane and binds to cardiolipin. In doing so, it helps recruit and stabilize other proteins and enzymes involved in energy production.

And I really want to emphasize how unique this is.

To have a peptide that can travel throughout the body, enter cells, home directly to mitochondria, and then stabilize these energy-producing “supercomplexes” (these assemblies of enzymes embedded in the membrane), that’s pretty remarkable.

FDA Approval for SS-31

But now let’s return to the recent FDA approval in this rare mitochondrial condition before broadening the discussion to more common chronic metabolic diseases.

The disease in question is called Barth syndrome.

It’s a 1 in a million genetic disease linked to a gene on the X chromosome, so it primarily affects males. At its core, it’s a disorder of mitochondrial cardiolipin metabolism.

In many ways, it’s human proof that if you don’t have sufficient functional cardiolipin, your mitochondria fail.

Barth syndrome is characterized by problems with the heart, skeletal muscle dysfunction, growth abnormalities, and a host of other complications, with many children requiring heart transplants by their teenage years.

So, researchers conducted a randomized, double-blind, placebo-controlled trial lasting 28 weeks, followed by a 168-week extension period.

The primary endpoint was safety and tolerability of SS-31, with secondary endpoints focused on functional outcomes, including fatigue scores and the six-minute walk test.

To cut to the chase: the SS-31 peptide was found to be safe, and it led to significant improvements in physical function, including fatigue and performance on the 6-minute walk test.

The 6-minute walk test is exactly what it sounds like: it measures how far a person can walk on a flat, hard surface in six minutes, serving as a proxy for functional aerobic capacity and endurance.

In general, an improvement of 25 to 35 meters is considered clinically meaningful.

In this trial, SS-31 led to a 96.1-meter improvement.

That’s a substantial signal, and clear evidence of improved physical function in patients with this mitochondrial disease. These benefits extended to fatigue scores, muscle strength, and other functional measures.

In short, this simple peptide, by helping to partially restore mitochondrial function, improved global physical performance, as well as signs and symptoms, in boys with Barth syndrome.

But there’s roughly a 0.0001% chance you have Barth syndrome.

So, you’re probably wondering whether SS-31 has any relevance for you or me?

The honest answer is SS-31 almost certainly matters for far more than the condition it was approved to treat.

In the rest of this letter for StayCurious Metabolism Premium members, we’ll dive into:

• Potential use cases for SS-31

  • Heart disease

  • Diabetes & diabetic complications

  • Alzheimer’s & Parkinson’s disease

• The future of mitochondrial medicine, including mitochondrial transplantation

• The two main classes of peptide suppliers

  • How I’m sourcing my peptides

This isn’t about prescriptions—it’s about information. I know a lot of you are interested in this topic, so we may as well practice “informed compounding.”

Now, come find out why Stay Curious Metabolism is a Top 3 Bestselling Science Newsletter Globally, and why members call it a staple in their health routines.