EMBRACE-STEMI™

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General Information

Bendavia is Stealth Peptides’ lead compound. It is named after the German physician, Dr. Carl Benda. In 1898, Dr. Benda coined the term mitochondria which was derived from the Greek terms ‘mitos’ (thread) and ‘chondros’ (granules), which describe the appearance of the mitochondrion as viewed during early cellular development. Stealth’s Bendavia targets the mitochondria (Benda) to protect cells from undergoing cellular death (via is the Roman term for life).

Due to Bendavia’s ability to penetrate epithelial monolayer cultures with tight junctions, it appears that there is transcellular transport of the molecule. In vitro studies of Bendavia have shown that the compound concentrates in the mitochondria at levels between 1,000 and 5,000 that measured in the extra-mitochondrial space. This compound appears to have minimal effects on cell cultures in which it has been tested. However, it prevents a variety of mitochondrial abnormalities  when the cells are disrupted by a variety of oxidative agents including hydrogen peroxide, peroxynitrite, tert-butyl hydroperoxide and 1-methyl-4-phenyl-1,2,3,6-tetrahydrapyridine. Following insults with these agents, Bendavia has been shown to profoundly ameliorate:

  • Uncoupling of the electron transport chain
  • Loss of the electrochemical potential (ΔΨm) across the mitochondrial membrane
  • Loss of ATP
  • Swelling of the mitochondria
  • Release of cytochrome c into the cytoplasm
  • Increase in intracellular reactive oxygen species (ROS)
  • Increase in lipid peroxidation
  • Increase in upregulation of heme-oxygenase-1
  • Increase in apoptosis as determined by caspase-3 increase and TUNEL positive cells
  • Increase in necrotic cells
  • Overall decreased cell survival

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As detailed in the “Ischemia Reperfusion Injury (IRI)” section, these abnormalities appear to be central to the development of reperfusion injury. Increasing animal data (see “Bendavia in IRI”) support that Bendavia can reduce the degree of damage following re-establishment of coronary blood flow to the heart at extremely low doses and systemic concentrations. Although acute myocardial infarction is the initial targeted indication for Bendavia, the compound has beneficial effects in a wide range of models as might be expected since mitochondrial dysfunction is a critical component of most pathophysiologic processes. Benefit has also been shown in animal models of stroke, acute renal injury due to ischemia, pancreatic islet cell transplantation, neurodegenerative diseases (Alzheimer’s disease, amyotrophic lateral sclerosis and Huntington’s disease), radiation exposure, drug-induced tissue injury (radio-contrast agents, cis-platin, aminoglycosides and acetaminophen), diabetic renal and peripheral nerve complications, diabetic retinopathy, macular degeneration, and cataract formation.