Potential uses of new human erythropoietin (hEPO)-derivatives for the treatment of neurodegenerative diseases

BÜRGI, M ; APARICIO, G ; KRATJE, ; R. SCORTICATI, C ; OGGERO, M

Villa Carlos Paz

Congreso; Reunión Anual de la Sociedad Argentina de Neurociencias (SAN) 2019; 2019

Sociedad Argentina de Investigación en Neurociencias

Neurodegenerative diseases are pathologies characterized by the progressive degeneration of the structure and function of the central or peripheral nervous system. Despite of the increasing number of people suffering these illnesses, non-effective treatments are available nowadays. Researchers are involved in the development of neuroprotective and/or neurotropic agents. In this area, EPO plays an important role due to its ability to develop a wide range of cellular responses in the brain, directly related to the protection and repair of cell damage. Nevertheless, its hematopoietic activity (HA) must be considered as a side effect.We developed new hyper-N-glycosylated hEPO-derivatives by introducing N glycosylation potential sites in those regions of the hEPO molecule identified as essentials for displaying the HA but not disturbing residues that are needed to retain their neuroprotective action and neuroplasticity.Three EPO variants were produced and purified with a purity level higher than 89%, showing an apparent molecular mass higher than EPO and a superior number of acidic isoforms as result of the increased glycosylation degree. The in vitro and the in vivo HA of each EPO analogue was abolished (p