SS31

The ss31 peptide (also known as Bendavia, MTP-131, or Elamipretide) is a significant synthetic mitochondrial-targeting peptide that has been extensively studied for its potential to treat diseases involving mitochondrial dysfunction.

Here’s a detailed breakdown of what you need to know:

What is ss31?

It is a small, water-soluble, aromatic-cationic tetrapeptide with the sequence 

D-Arg-Dmt-Lys-Phe-NH₂ (where Dmt is 2',6'-dimethyltyrosine). Its key features are:

• Mitochondrial Targeting: It is designed to freely cross cell membranes and accumulate several hundred-fold within the inner mitochondrial membrane (IMM), driven by the large negative charge (ΔΨm) inside.

• Mechanism of Action: It binds to cardiolipin, a unique phospholipid found almost exclusively in the IMM. Cardiolipin is crucial for the structure and function of mitochondrial electron transport chain (ETC) complexes. In conditions of stress, cardiolipin can be oxidized and lose its association with ETC proteins, leading to inefficiency and reactive oxygen species (ROS) production.

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• Primary Proposed Mechanisms & Benefits

  By interacting with cardiolipin, ss31 is believed to:

  Stabilize Electron Transport Chain Supercomplexes: Improves the efficiency of cellular respiration (ATP production) and reduces electron "leakage."

  Reduce Oxidative Stress: By making the ETC more efficient, it drastically lowers the production of damaging reactive oxygen species (ROS).

  Inhibit Mitochondrial Permeability Transition Pore (mPTP) Opening: Helps prevent the collapse of mitochondrial function and the initiation of apoptosis (cell death).

  Improve Mitochondrial Fusion/Fission Dynamics: Promotes healthier mitochondrial networks.

  Primary Areas of Research & Clinical Trials

  ss31 has been investigated in a wide range of conditions where mitochondrial dysfunction is a key player:

• Cardiovascular:

  • Myocardial Infarction (Heart Attack): To reduce reperfusion injury when blood flow is restored.

  • Heart Failure: To improve the energy-deficient state of failing heart cells.

• Neurodegenerative Diseases:

  • Alzheimer's Disease: To improve neuronal bioenergetics and reduce oxidative damage.

  • Parkinson's Disease: To protect dopaminergic neurons.

  • Huntington's Disease: Models showed improved motor function and survival.

• Ocular Diseases:

  • Dry Age-Related Macular Degeneration (AMD): The most advanced clinical program. A topical eye drop formulation (SPI-1005) showed promise in improving visual function in a Phase 2 trial.

• Mitochondrial Myopathies: Such as Barth Syndrome, a genetic disorder linked to cardiolipin metabolism.

• Acute Kidney Injury: To protect renal tubule cells during ischemia.

• Aging & Frailty: To address the fundamental role of mitochondrial decline in aging.

Clinical Trial Status & Challenges

• Mixed Results: While preclinical data in animal models has been overwhelmingly positive, human clinical trials have shown modest and variable results.

• Important Considerations and Cautions

• Side Effects: In clinical trials, it was generally well-tolerated. Reported side effects were often mild and included reactions at the infusion/injection site, dizziness, and gastrointestinal symptoms. However, the long-term safety profile is not fully known.

• Do Not Self-Experiment: Self-administration of research-grade ss31 is strongly discouraged due to significant risks and lack of proven efficacy for any off-label use.

• Summary

  ss31 is a groundbreaking research tool that has taught us a great deal about targeting mitochondrial dysfunction. It holds significant therapeutic promise, particularly for age-related and degenerative diseases. However, the translation from compelling lab science to effective human therapy has proven difficult. Its future depends on the outcomes of ongoing and future clinical trials, with the eye drop formulation for dry AMD currently being the most advanced and hopeful pathway.

  If you are interested in this for research, always source materials from reputable suppliers. If you are a patient seeking treatment, discuss ongoing clinical trials (clinicaltrials.gov) with your physician.

• Key Failure: A large Phase 3 trial (ATTACH) in patients with acute heart failure did not meet its primary endpoint, dealing a major setback.

• Current Focus: The most promising recent results are in ophthalmology (dry AMD). Development for other indications continues but faces challenges in trial design and demonstrating clear efficacy.

• Administration: Early trials used intravenous infusion. Newer formulations (like subcutaneous injection and topical eye drops) are being developed.