Detection of a non-erythropoietic EPO, Neuro-EPO, in blood after intra-nasal administration in rat.
Fiche publication
Date publication
août 2020
Journal
Drug testing and analysis
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MARTIN Laurent
Tous les auteurs :
Martin L, Rodriguez JCG, Audran M, Ericsson M, Maurice T, Marchand A
Lien Pubmed
Résumé
Non-erythropoietic erythropoietin (EPO) are investigated for their high anti-oxidant properties. A new drug candidate under clinical investigation to treat brain diseases is Neuro-EPO, produced by selecting EPO isoforms with low sialic acid content. Intra-nasal administration allows to bypass the blood-brain barrier to get a fast and concentrated delivery to the brain. The aims of this project were to characterize Neuro-EPO with anti-doping methods used to detect conventional recombinant EPOs (IEF and SDS-PAGE) and to evaluate the window of detection of Neuro-EPO in brain and blood (plasma) after a single intranasal administration in rats. Neuro-EPO drug analyzed by IEF-PAGE presented a very basic profile completely detected only when using a 2-8 o 2-10 pH gradient instead of the conventional 2-6 pH gradient. Its profile consisted in 6 main bands that did not interfere with endogenous EPO profile from human or rat. After SDS-PAGE, a broad band was detected for Neuro-EPO in the same area as endogenous EPO, making Neuro-EPO identification very difficult by this appraoch. Therefore, IEF was the method for identification chosen after administration in rats. Neuro-EPO was clearly identified in blood 2h and 6h after the delivery. Fainter signals were obtained between 12h and 48 h, but some characteristic very basic bands remained detectable. Surprisingly, brain extracts did not show the presence of Neuro-EPO even 2 hours after administration, indicating a fast degradation or elimination from the brain to the bloodstream. This experiment indicated that detection of Neuro-EPO after intranasal delivery should be possible for a few days.
Référence
Drug Test Anal. 2020 Aug 27;: