2115

S1PR3 Biologics Therapy for Severe Sepsis, Ebola and Swine-flu Conditions

Ben-Sasson Shmuel, HUJI, School of Medicine - IMRIC, Developmental Biology and Cancer Research

 

Category

Medical Sciences, Peptide protein

Highlights

Increased blood vessel permeability and vascular leak are a final common pathway in severe influenza and other fatal diseases, such as MERS, Ebola and sepsis. A novel biologics therapy enables to tighten blood vessels and prevent death.

  • Our finding uncovers an unprecedented function of S1PR3 receptor in anti-infectious immunity, which may have clinical implications.
  • The preclinical data implies that pharmaceutical agents targeting S1PR3 may have beneficial value for septic patients.

Our Innovation

  • Our finding uncovers an unprecedented function of S1PR3 receptor in anti-infectious immunity, which may have clinical implications.
  • The drug is a short peptide including several chemical modifications. This decoy biologics is derived from a distinct trans-membrane receptor, S1P3, which regulates vascular permeability. Thus, S1P3 activation overcomes pathological vessel leakage (
  • Effect demonstrated at the molecular and cellular level.

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Figure 1: S1PR3 deficiency increases susceptibility to sepsis. (A) S1PR3-/- (n=30) and WT (n=27) mice were subjected to CLP (cecal, ligation and puncture), and mouse survival was monitored. The lungs (B) and livers (C) were subjected to H&E staining, and lung injury score were assessed (B, right)

2115-fig3.jpg 

Figure 3:  The killing of internalized E-coli in peritoneal macrophages from S1PR3-/- and WT mice, as assessed by gentamycin protection assay (n=4 each)

Current Development Stage      

TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model

  • In vivo evidence was provided for a protective role of S1PR3 peptide against in multiple models of sepsis in wild-type but not macrophage-specific Vps34 mice.
  • It was demonstrated that enhancement of S1PR3 activity facilitates macrophage bactericidal killing and protects mice against sepsis.

The Opportunity

Sepsis is defined as life-threating organ dysfunction caused by a dysregulated host response to infection. It is the leading cause of death with morality rates up to 40-50%. So far, anti-sepsis treatment modalities are rather limited, and sepsis remains one of the most pressing public health burdens worldwide.

Patent Status

Published CN 105873944 A

Granted US 9,873,724

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
+972-2-6586608
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