What is Elamipretide used for?

Elamipretide (also known as SS-31, , MTP-131 and Bendavia) is a small mitochondrially-targeted tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that appears to reduce the production of toxic reactive oxygen species and stabilize cardiolipin.

Stealth Peptides, a privately held company, was founded in 2006 to develop intellectual property licensed from several universities including elamipretide; it subsequently changed its name to Stealth BioTherapeutics.

Elamipretide: a mitochondrial protector

Mitochondrial dysfunction has been implicated in the pathogenesis of numerous diseases, and elamipretide is essentially a mitochondrial protector that has been studied in many ocular and nonocular diseases, such as Fuchs dystrophy, heart failure, mitochondrial myopathy, and even rare cardiomyopathies such as Barth syndrome.  Subcutaneous administration of elamipretide (MTP-131; Stealth BioTherapeutics Inc) to treat noncentral geographic atrophy in age-related macular degeneration (AMD) has been developed to restore mitochondrial function and morphology and offers promising potential as a treatment for geographic atrophy (GA).

The therapeutic effect of elamipretide occurs via restoration of mitochondrial bioenergetics, which is under study in ocular and nonocular diseases.

Application in treating Primary mitochondrial disorders

Primary mitochondrial disorders (PMDs) are a heterogeneous group of genetic diseases causing impaired mitochondrial respiration1,–5 and are considered among the most common inherited metabolic disorders in humans, with a prevalence in adults of ≈1 in 4,300. PMDs can affect almost any organ but mostly affect those with high energy demands (nervous system, skeletal muscle, heart, kidney, and retina). PMDs cause several well-recognized syndromes, with muscular involvement being common in the adult patient. In a survey of 290 patients with PMD, muscle weakness, chronic fatigue, exercise intolerance, gastrointestinal problems, and balance problems were the 5 most common symptoms experienced in >75% of patients. Primary mitochondrial myopathy (PMM) is a PMD affecting predominantly, but not exclusively, skeletal muscle. PMM can be very disabling and adversely affects patients' quality of life with no available treatments to be used aside from palliative approaches.

Elamipretide is an aromatic-cationic tetrapeptide that readily penetrates cell membranes and transiently localizes to the inner mitochondrial membrane where it associates with cardiolipin. Through this mechanism of action, elamipretide is thought to restore energy production, to reduce the production of reactive oxygen species, and ultimately to increase the energy (adenosine triphosphate [ATP]) supplied to affected cells and organs. In preclinical studies, elamipretide increased the synthesis of ATP and reduced reactive oxygen species production regardless of the specific mitochondrial abnormality causing the impaired mitochondrial respiration. There is no observed effect on normally functioning mitochondria.

Mechanism of Action

Elamipretide, is a peptide compound that readily penetrates cell membranes, and targets the inner mitochondrial membrane where it binds reversibly to cardiolipin. In preclinical or clinical studies, we have observed that elamipretide increases mitochondrial respiration, improves electron transport chain function and ATP production and reduces formation of pathogenic ROS levels. This elamipretide-cardiolipin association has been shown to normalize the structure of the inner mitochondrial membrane, thereby improving mitochondrial function. Functional benefit is achieved through improvement of ATP production and interruption and potential reversal of damaging oxidative stress.

As of November 2017 Stealth had obtained an orphan designation in the US for use in mitochondrial myopathy and had started a Phase III trial in that indication. As of January 2020, trial expectations were not met.

You may like