Affiliations: Center for Genetic Engineering and Biotechnology, Cubanacan, Playa, Havana, Cuba | Center of Molecular Immunology, Atabey, Playa, Havana, Cuba | Institute of Neurology and Neurosurgery, Vedado, Havana, Cuba | Pathology Department of Institute of Nephrology , Havana, Cuba
Note: [] Corresponding author: Diana García del Barco MD, Pharmaceutical Division, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave.31 e/158 & 190 P.O. Box 6162. Cubanacan, Playa 10600, Havana, Cuba. Tel.: +53 7 2716022; Fax: +53 7 273 1779; E-mail: [email protected]
Abstract: Purpose: Multiple sclerosis is a complex and devastating autoimmune disease of the central nervous system. Up to now, a constellation of candidate drugs have been evaluated with no major success. Experimental Autoimmune Encephalitis (EAE) is the animal counterpart that reproduces critical features of the human MS process. The aim of the present work is to study a possible therapeutic effect of epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP6 coadministration in mild and severe EAE. Methods: Mild and severe forms of EAE were generated immunizing rats and mice with xenogeneic spinal cord homogenate and with the encephalitogenic peptide MOGp35–35, respectively. EGF and GHRP6 alone or combined were administered in therapeutic and prophylactic schedules. A clinical score was established to follow-up the animals during the disease period. Malondialdehyde (MDA) serum concentration and insulin like growth factor-1 (IGF-1) relative level from brain tissue were determined. Results: Only the combined EGF+GHRP6 therapy reduced the clinical score in mild as well in severe EAE forms. The combination also improved the survival rate in nearly 100% of the severe EAE animals. In addition to these effects, there was an increase in the brain IGF-1 transcript and a decrease of serum MDA. Conclusions: EGF+GHRP6 proved to be effective in improving the natural course of both mild and severe EAE. Accordingly, the treatment reduces inflammatory infiltration and microvascular damage, which may be associated to the attenuation of the lipid peroxidation process and the transcriptional enhancement of IGF-1, a major pro-survival factor for brain cells.
