Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.

Le 01 Avr 2024

Auteur : Correa-Paz C, Pérez-Mato M, Bellemain-Sagnard M, González-Domínguez M, Marie P, Pérez-Gayol L, López-Arias E, Del Pozo-Filíu L, López-Amoedo S, Bugallo-Casal A, Alonso-Alonso ML, Candamo-Lourido M, Santamaría-Cadavid M, Arias-Rivas S, Rodríguez-Yañez M, Iglesias-Rey R, Castillo J, Vivien D, Rubio M, Campos F

Année : 2024

Journal : J Cereb Blood Flow Metab 1559-7016

PubMed Id : 38436292

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.