BACKGROUND:  Injuries to the brain or spinal cord from stroke, trauma or neurodegenerative disease produce a limited reparative response and minimal functional recovery. Current treatment for such injuries is limited to physical rehabilitation and acute intravenous administration of a thrombolytic drug called tissue plasminogen activator (tPA). tPA dissolves blood clots, opens brain blood vessels, and has a modest behavioral benefit in functional recovery. However, tPA has a narrow therapeutic window and it must be delivered within 3 hours from the time a patient suffers a stroke, otherwise risks outweigh the benefits. tPA is not a repair or rehabilitative treatment, but a tissue protection treatment. At the present time, there is no approved pharmacological therapy that promotes tissue repair and recovery after a central nervous system injury.

INNOVATION:  Researchers at UCLA have identified a novel pharmacological treatment that targets molecular interactions involving a group of molecules called ephrins. The ephrinA system is important in the developing body for brain development and blood vessel development, but has no known role in normal body function in the adult. However, during post-stroke healing, ephrins have been shown to block neural repair. This new treatment prevents ephrins from blocking axonal sprouting, allowing axonal reconnection in the brain after injury and promoting behavioral recovery. The ephrin blocker can be administered in different forms and pathways, including a cannula implant or hydrogel, which can be locally delivered using common operating room techniques. It can also be administered systemically through a blood-brain barrier permeable therapy, such as an insulin or transferrin receptor linker protein.

POTENTIAL APPLICATIONS 

• Promotes axonal sprouting in the brain and improves functional recovery after stroke
• Can be adapted to aid in the repair of other sources of neural injury, such as spinal cord injury

ADVANTAGES

• Novel pharmacological therapy to promote neural repair and recovery in stroke
• Manipulates a biological system with expected low side effects
• Administered at a delay after stroke, when patient is stable and directed towards recovery and repair
• Multiple delivery pathways

DEVELOPMENT-TO-DATE:  This treatment has been tested in in vitro and in vivo preclinical stroke systems in two different stroke models in mice. Multiple delivery methods have been tested for the administration of the blockade. All tests have shown efficacy in promoting axonal sprouting, and the preclinical studies in vivo have shown that behavior recovery is substantial early during the recovery process, and continues to increase in magnitude of recovery with the length of drug delivery.

Reference: UCLA Case No. 2009-184