Cofilin inhibitor for the treatment of hemorrhagic brain injury-induced inflammation

Description:

Project ID D2019-35

Background

Cofilin regulates actin filament assembly and organization in most cells, including during macrophage, T-cell, and dendritic activation and migration. Over-activation of cofilin can lead to microglia inflammation in the brain. Although Cofilin has been shown to be involved in the secondary injury of intracerebral hemorrhage (ICH), there has been no effective therapy to date. Current cofilin inhibition tactics include the use of gene deletion, which has many drawbacks such as high cost value, and risk of immune reactions and other off target effects.  Therefore, there is a need to develop a small molecule cofilin inhibitor which can inhibit cofilin-mediated microglial activation and neuroinflammation.

Invention Description

Researchers at the University of Toledo have developed SZ-3, a first-in-class inhibitor for Cofilin. Neuroprotective properties of SZ-3 significantly reduced cofilin expression and NO release. SZ-3 also was shown to reduce proliferation and migration of microglial cells and attenuate LPS-induced microglial activation and inflammation. In mice with collagenase-induced hemorrhage, SZ-3 was capable of reducing behavioral deficits with both the experimental and the sham animals showing an improvement in grip strength and motor activity.

Applications

  • Treatment of secondary brain injury related neuroinflammation
  • Recovery enhancement
  • Enhancement of motor function and muscle strength

Advantages

  • Satisfies an unmet need in the stroke patient population
  • Considers the ensuing secondary injury of ICH that results in higher mortality rates

IP Status:      U.S. Patent # 11548850

Patent Information:
For Information, Contact:
Katherine Pollard
Licensing Associate
The University of Toledo
419-530-6228
katherine.pollard@utoledo.edu
Inventors:
Zahoor Shah
Saleh Alaqel
Liyanaaratchige Tillekeratne
Keywords:
Cofilin
Hemorrhagic
Stroke