Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice

• Published in: Scientific reports 2019-10, Vol.9 (1), p.12876-12, Article 12876
• Main Authors: Hayrabedyan, Soren, Shainer, Reut, Yekhtin, Zhanna, Weiss, Lola, Almogi-Hazan, Osnat, Or, Reuven, Farnsworth, Charles L., Newsome, Scott, Todorova, Krassimira, Paidas, Michael J., Brodie, Chaya, Barnea, Eytan R., Mueller, Martin
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/105; 631/337/458; 631/378/2606/1666; 82/47; Animal models; Animals; Blood-brain barrier; Brain injury; Calcium; Cyclic AMP; Encephalitis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental allergic encephalomyelitis; Female; Humanities and Social Sciences; Immunoregulation; Inflammation; Kinases; Mice; multidisciplinary; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Myelination; Neurodegeneration; Paralysis; Paralysis - drug therapy; Paralysis - metabolism; Paralysis - pathology; Peptides - pharmacokinetics; Peptides - pharmacology; Post-translation; Pregnancy; Protein kinase A; Protein kinase C; Protein Processing, Post-Translational - drug effects; Proteins; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48473-x

An autoimmune response against myelin protein is considered one of the key pathogenic processes that initiates multiple sclerosis (MS). The currently available MS disease modifying therapies have demonstrated to reduce the frequency of inflammatory attacks. However, they appear limited in preventing disease progression and neurodegeneration. Hence, novel therapeutic approaches targeting both inflammation and neuroregeneration are urgently needed. A new pregnancy derived synthetic peptide, synthetic PreImplantation Factor (sPIF), crosses the blood-brain barrier and prevents neuro-inflammation. We report that sPIF reduces paralysis and de-myelination of the brain in a clinically-relevant experimental autoimmune encephalomyelitis mice model. These effects, at least in part, are due to post-translational modifications, which involve cyclic AMP dependent protein kinase (PKA), calcium-dependent protein kinase (PKC), and immune regulation. In terms of potential MS treatment, sPIF was successfully tested in neurodegenerative animal models of perinatal brain injury and experimental autoimmune encephalitis. Importantly, sPIF received a FDA Fast Track Approval for first in human trial in autommuninty (completed).