A Robarts' Scientist has generated a target-based primary in vitro cell-based screen for evaluating compounds or peptides affecting scar matrix deposition and remodeling during wound repair.

BACKGROUND: There has been a general shift in the search to identify candidate therapeutics to earlier stage functional screening of compound libraries. Early concept stage screening of compounds for potential therapeutic application is one of the most critical stages in drug development and represents a market of over USD$1.2B/yr.  To be effective, the functional assay must be relatively simple, reproducible, very high throughput, relevant to the system to be evaluated, and limit false positives and false negatives.  The ideal target system must converge on an appropriate target that represents a near critical regulator of a phenotype.  Identification of the appropriate high throughput assay can reduce the risk in drug discovery, eliminate irrelevant targets, and reduce the financial burden.

The market of augmenting wound repair and regeneration is estimated at USD$13B and includes central nervous system repair following injury or stroke, the skin repair, and ophthalmic applications.  Between these systems are distinct commonalities in the mechanism of scar formation and aberrant extracellular matrix remodeling.  Screening compounds affecting any of these systems are often dependent upon modeling therapies that target one of either scar formation or regeneration.  The range of assays include in silico modeling, monolayer cell based assays, or 3D tissue models.  Each method may have limitations in resolution, scope, high through-put capacity, or in the potential to evaluate a defined and relevant outcome.  The identification of a target indicator gene that modulates the generation of scarring versus regenerative remodeling conditions would represent an advancement in high throughput functional screening systems for wound repair and regeneration. 

DESCRIPTION OF THE INVENTION:  A Robarts’ Scientist has generated a target-based primary in vitro cell-based screen for evaluating compounds or peptides affecting scar matrix deposition and remodeling during wound repair. The reporter provides an indicator of the activity of a validated modulator of scar generation and remodeling within a multitude of cell systems. The output of the screen is versatile and may include of the evaluation of the genetic targets of the protein, the matrix resulting from the target protein’s activation, and/or the activation of the reporter. Finally, the system is applicable for many cell types and systems including dermal fibroblasts, corneal stromal cells, neural astrocytes, and vascular fibroblasts.

POTENTIAL ADVANTAGES/USES:

• Was primarily developed to regeneration in spinal cord and post-stroke repair
• The target gene has minimal critical background function in adulthood
• The reporter concept is well established
• Can effectively screen libraries of compounds for potential to modulate scarring
• Readout can be evaluated by ELISA, real-time PCR, or plate reader
• Screen may be customized for skin, neural, or ophthalmic applications

DEVELOPMENT STAGE: In vitro proof of principle.

Keywords: Skin, Eye, CNS, Drug discovery, Compound library screen, Regenerative medicine, Transcription factor, Extracellular matrix, Scar, Wound repair

Phase I

This technology is covered under a PCT patent application.

Available for out-licensing. A collaborative research approach involving the inventor would also be considered.