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

Research output: Contribution to journalArticle

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 (US)
Article number12876
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Post Translational Protein Processing
Paralysis
Multiple Sclerosis
Proteins
Inflammation
Myelin Proteins
Autoimmune Experimental Encephalomyelitis
Cyclic AMP-Dependent Protein Kinases
Blood-Brain Barrier
Autoimmunity
Brain Injuries
Disease Progression
Animal Models
Pregnancy
Peptides
synthetic preimplantation factor
Brain
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Hayrabedyan, S., Shainer, R., Yekhtin, Z., Weiss, L., Almogi-Hazan, O., Or, R., ... Mueller, M. (2019). Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice. Scientific reports, 9(1), [12876]. https://doi.org/10.1038/s41598-019-48473-x

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

In: Scientific reports, Vol. 9, No. 1, 12876, 01.12.2019.

Research output: Contribution to journalArticle

Hayrabedyan, S, Shainer, R, Yekhtin, Z, Weiss, L, Almogi-Hazan, O, Or, R, Farnsworth, CL, Newsome, S, Todorova, K, Paidas, MJ, Brodie, C, Barnea, ER & Mueller, M 2019, 'Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice', Scientific reports, vol. 9, no. 1, 12876. https://doi.org/10.1038/s41598-019-48473-x
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. / Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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