Development of anti-ischemic molecules

Mitochondrial respiration is arrested by low oxygen tension and ATP content decreases when cells are exposed to hypoxia. We demonstrated that certain drugs used in the treatment of venous insufficiency or of peripheral arteriopathy can protect cells againt hypoxia because they enhance respiration activity even at low oxygen concentration. Using isolated mitochondria, we showed that some of the drugs protect the respiratory complexes I and III while others increase adenine nucleotide translocase activity. Bilobalide, a consituent of Ginkgo biloba extract, belongs to the first group. Based on these findings, we are currently developing new anti-ischemic drugs targeted toward the mitochondrial respiratory chain. Possible therapeutic indications include peripheral arteriopathy, mild cerebral ischemia, angina, as well as chronic venous insufficiency.