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

Soren Hayrabedyan, Reut Shainer, Zhanna Yekhtin, Lola Weiss, Osnat Almogi-Hazan, Reuven Or, Charles L. Farnsworth, Scott Newsome, Krassimira Todorova, Michael J. Paidas, Chaya Brodie, Eytan R. Barnea*, Martin Mueller*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

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).

Original languageEnglish
Article number12876
Number of pages12
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 2 Oct 2019

Keywords

  • KINASE-A
  • DISEASE
  • BRAIN
  • NEUROINFLAMMATION
  • NEUROPROTECTION
  • SYNDECAN-1
  • PREVENTS

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