CE18 - Innovation biomédicale

A new pharmacological opportunity in acute myocardial infarction by preventing activation of the translation initiation factor eIF5A – MOMI

Submission summary

Myocardial infarction, which is involved in 20% of deaths in Europe, corresponds to a blood flow arrest (= ischemia) that deprives the heart of its vital oxygen and nutrient requirements, the deleterious effects of which are time dependent. This is followed, spontaneously or after medical intervention, by a sudden return of blood flow (= reperfusion) and especially of oxygen leading to alterations of mitochondrial function and ionic homeostasis, and finally to cell death. Major advances in the management of infarction have been made and allow to limit ischemia time and death. Unfortunately, no treatment can reduce the deleterious effects of reperfusion and especially the development of heart failure in the longer term which is a big health problem. We have shown in ischemia/reperfusion (IR) preclinical models the efficacy of an eIF5A hypusination inhibitor, the GC7, in protecting organs against IR injury including the brain in stroke. GC7 is effective in pre- and post-treatment of ischemia and leads to increased survival and better functional recovery of the organ in both the short and long term. Treatment of a cardiomyocyte cell line with GC7 demonstrated protection against ischemia/reperfusion with a decrease in mitochondrial alterations and an improvement in ionic homeostasis. Moreover, in a mouse model of myocardial infarction, GC7 used 5 min before reperfusion decreased infarct size. We now need to confirm these results in more rigorous cellular and preclinical models, such as primary human cardiomyocytes, ex vivo model of isolated rat hearts, and an in vivo mouse myocardial infarction model considering gender, age and comorbidities, as pre-diabetic environment which is a major risk factor in humans. We want to demonstrate the efficacy of GC7 in limiting the infarct size and improving long term cardiac function by limiting heart failure and thus propose a new therapeutic option.

Project coordination

Didier PISANI (Laboratoire de Physio-Médecine Moléculaire)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CRMBM Centre de résonance magnétique biologique et médicale
LP2M Laboratoire de Physio-Médecine Moléculaire
CARMEN LABORATOIRE DE RECHERCHE EN CARDIOVASCULAIRE, METABOLISME, DIABETOLOGIE ET NUTRITION

Help of the ANR 564,792 euros
Beginning and duration of the scientific project: December 2023 - 48 Months

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