TY - JOUR
T1 - Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice
AU - Hayrabedyan, Soren
AU - Shainer, Reut
AU - Yekhtin, Zhanna
AU - Weiss, Lola
AU - Almogi-Hazan, Osnat
AU - Or, Reuven
AU - Farnsworth, Charles L.
AU - Newsome, Scott
AU - Todorova, Krassimira
AU - Paidas, Michael J.
AU - Brodie, Chaya
AU - Barnea, Eytan R.
AU - Mueller, Martin
N1 - Publisher Copyright: © 2019, The Author(s).
PY - 2019/10/2
Y1 - 2019/10/2
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=85072941353&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-019-48473-x
DO - https://doi.org/10.1038/s41598-019-48473-x
M3 - مقالة
C2 - 31578341
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12876
ER -