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 (2019). Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice. Scientific reports, 9(1), p. 12876. Springer Nature 10.1038/s41598-019-48473-x

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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).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Müller, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Springer Nature

Language:

English

Submitter:

Monika Zehr

Date Deposited:

27 Dec 2019 16:25

Last Modified:

28 Nov 2020 02:30

Publisher DOI:

10.1038/s41598-019-48473-x

PubMed ID:

31578341

BORIS DOI:

10.7892/boris.136824

URI:

https://boris.unibe.ch/id/eprint/136824

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