BSY12: A PROMISING MOLECULE FOR NEUROLOGICAL DISORDERS

SCORTICATI, CAMILA; OGGERO EBERHARDT, MARCOS; BÜRGI, MARÍA DE LOS MILAGROS; KRATJE, RICARDO; DEPETRIS, MATÍAS

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Neurological disorders (ND) include a wide range of pathologies affecting people´s life quality. In 2019, 1.5 billion people worldwide were diagnosed with some ND, which are expected to increase about 12% by 2030. Nowadays there are no effective treatments to slow their progression. Erythropoietin (EPO) represents a promising candidate considering its neurobiological action (NA). Nevertheless, its erythropoietic activity (EA) triggers undesirable effects. Consequently, we developed an EPO-derivative (BSY12) through glycoengineering to block the EA while preserving the NA. BSY12 was produced by CHO.K1 cells, immunoaffinity chromatography-purified and widely characterized. The protein structure and stability were evaluated by circular dichroism and thermal shift analysis. The EA, analyzed as the hematocrit increment, was evaluated in normocytic BALB/c mice. The BSY12 antiapoptotic capacity was studied in primary cultures of hippocampal neurons. Additionally, a Sholl analysis in CA1 pyramidal neurons of the hippocampus from BSY12-treated CF1 mice were carried out. The ability to cross the blood brain barrier (BBB) was studied in CF1, C57BI/6N and SOD1G93A mice. The in vivo neurobiology performance was evaluated through the Complex Running Wheels test in healthy C57BI/6N mice and in a model of amyotrophic lateral sclerosis using SOD1G93A mice. BSY12 presented a partially-folded structure. The EA was blocked but its NA was preserved taking into account that in hippocampal neurons, BSY12 reduces their in vitro staurosporine-induced apoptosis and increases their total dendrite extension and dendritic brunch intersections in vivo (p