Technology Listings


Repurposed Therapeutic for Treating Infection-Sensitized Neonatal Encephalopathy

Application

New use of fingolimod (GilenyaTM) to treat infection-sensitized neonatal hypoxic-ischemic encephalopathy (HIE) via inhibition of Sphingosine-1-Phosphate receptor (S1PR) activation.

Key Benefits
  • Has been shown to reduce inflammatory markers and brain loss in rat models of infection-sensitized hypoxia ischemia.
  • Could be used to treat infection-sensitized neonatal encephalopathy, a condition with an unmet need.
  • Is FDA approved to treat multiple sclerosis which potentially reduces regulatory hurdles.
Market Summary

In the developed world, the incidence of severe perinatal asphyxia leading to neurological impairment or death is roughly 1/1000 live births. This rate rises dramatically to ~1/100 live births however when only the developing world is considered. Further, infection of the fetal membranes due to bacterial infection (chorioamnionitis) is relatively common at ~14% of births in the US. When taken together, the prevalence of perinatal asphyxia and chorioamnionitis indicate that infection-sensitized neonatal HIE is a major health concern. Currently there are no therapies on the market and few in development to treat this condition.

Technical Summary

Hypoxic-ischemic encephalopathy (HIE) arises when there is a lack of oxygen to the brain caused by almost any reduction in blood flow. Morbidities associated with this condition include intellectual disabilities, seizures and cerebral palsy. One of the subsets of this condition is neonatal HIE. Blood flow can be reduced for a number of reasons before, during and after birth; but, infection of the amnion (chorioamnionitis) has been repeatedly correlated with an increased severity in HIE. This situation is called infection-sensitized HIE. Emory inventors have discovered that S1PR is a key component of mediating the inflammatory response involved in infection-sensitized HIE. Antagonizing the S1PR with fingolimod was shown to reduce brain loss in a rat pup lipopolysaccharide model of inflammation where blood flow was reduced to the brain via carotid ligation. Additionally, inflammatory markers such as microglial activation and NF-κB, were significantly reduced. The reduced brain atrophy and inflammation exhibited in rat pups treated with fingolimod suggest that the compound can be used to reduce morbidity in neonatal infection-sensitized HIE.

Patent Information
App Type Country Serial No. Patent No. File Date Issued Date Expire Date
Utility(parent) United States 14/716,007 5/19/2015    
Tech ID: 13199
Published: 7/31/2014
Category
Therapeutics

Contact
Cliff Michaels
Assistant Director
Emory University
404-727-3890
ccmicha@emory.edu

Inventor(s)
Chia-Yi (Alex) Kuan
Dianer Yang
Yu-Yo Sun

Keywords
Repurposed Drug
Neuroscience/Pain
Microbiology/Infectious Diseases