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Bamberger 2018 MiP2018

From Bioblast
Discovery and development of elamipretide: targeting mitochondrial dysfunction in rare and common disease.

Link: MiP2018

Bamberger M (2018)

Event: MiP2018


Mitochondrial dysfunction is the primary cause or secondary complication of multiple diseases, both rare and common. Primary mitochondrial diseases include Leigh syndrome, MELAS, Barth syndrome (BTHS), Leber Hereditary Optic Neuropathy (LHON) and Primary Mitochondrial Myopathy (PMM) among others. Data also strongly points to aberrant mitochondrial function in many common age-related diseases, such as skeletal muscle loss (sarcopenia), kidney and heart disease, Age Related Macular Degeneration (AMD), and several neurodegenerative diseases such as Parkinson’s, Huntington’s, Alzheimer’s and ALS. Elamipretide (aka SS-31) is a member of a class of tetrapeptides containing an aromatic-cationic motif that target the inner mitochondrial membrane (IMM) via a reversible interaction with the phospholipid cardiolipin. Multiple peer-reviewed publications demonstrate that elamipretide consistently improves mitochondrial, cellular, and organ function in both in vitro and in vivo disease models for which mitochondrial dysfunction is understood to be an important component, and can reduce downstream consequences of mitochondrial dysfunction including fibrosis, inflammation and cell death. Elamipretide is currently in clinical development for PMM, BTHS, LHON, and AMD.

Current data support a mechanism of action that by binding to cardiolipin, elamipretide stabilizes and restores the physical structure and biochemical properties of the IMM, keeping the individual electron chain transport complexes in close proximity to one another, enhancing supercomplex formation, increasing respiratory function and ATP production, while decreasing reactive oxygen species (ROS) generation. The structure-activity relationship of the binding to cardiolipin and ability to impact respiration, ATP and ROS production has been studied resulting in multiple chemical classes of compounds with different physical, ADME and PK properties.

Bioblast editor: Plangger M, Kandolf G

Labels: MiParea: Respiration, mt-Membrane, Pharmacology;toxicology 

Stress:Mitochondrial disease 

Regulation: ATP production 



Stealth BioTherapeutics, Newton, MA, USA. - [email protected]