Compositions and methods for treating central nervous system injury
Inventors
Tomlinson, Stephen • ADKINS, DeAnna • Alawieh, Ali
Assignees
MUSC Foundation for Research and Development • US Department of Veterans Affairs
Publication Number
US-11806389-B2
Publication Date
2023-11-07
Expiration Date
2037-10-17
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention describes compositions and method for improving outcomes after injury to the central nervous system wherein complement signaling is activated. In one aspect, the method comprises administering to a subject a therapeutically effective amount of a therapeutic agent comprising a targeted inhibitor molecule comprising a targeting portion and an inhibitor portion, wherein the molecule inhibits complement, and wherein therapeutic agent is administered in combination with rehabilitation therapy or thrombolytic agent.
Core Innovation
The invention provides compositions and methods for improving outcomes after injury to the central nervous system wherein complement signaling is activated. The invention includes administering a therapeutically effective amount of a therapeutic agent comprising a targeted inhibitor molecule with a targeting portion and an inhibitor portion that inhibits complement signaling. This therapeutic agent is administered in combination with rehabilitation therapy or a thrombolytic agent.
The method enhances functional recovery by combining complement inhibition with standard therapies such as rehabilitation or thrombolytic agents. The targeted inhibitor molecules specifically bind to targets such as Annexin IV, post-translational modifications of Annexin IV, or phospholipids. The inhibitor portion can be selected from several complement inhibitors like Factor H, DAF, MCP, CD59, Crry, MAp44, and CR1. The therapeutic agent can be administered even several hours after injury, increasing the treatment window compared to standard care.
The problem being solved is the need for improved compositions and methods for treating central nervous system injuries such as ischemic stroke, traumatic brain injury, and spinal cord injury. Ischemic stroke is a leading cause of death and disability, and existing treatments require very early administration. Complement activation plays a central role in ischemia reperfusion injury, and systemic complement inhibition has drawbacks including immunosuppression and limited efficacy. Therefore, the invention addresses the need to effectively inhibit complement activation at the injury sites in a targeted way to reduce secondary injury, improve survival, and enhance motor and cognitive recovery, while enabling combination with standard therapies.
Claims Coverage
The patent includes one independent claim directed to a method of treating central nervous system injury by administering a composition comprising a targeted inhibitor molecule and providing rehabilitation therapy. The claim covers the targeting portion, the complement inhibitor, the type of injury treated, and the rehabilitation therapy.
Method of treating central nervous system injury with targeted inhibitor and rehabilitation therapy
A method comprising (a) administering a therapeutically effective amount of a composition with a targeted inhibitor molecule that includes a targeting portion and a complement inhibitor, and (b) providing rehabilitation therapy to the subject.
Targeting portion that specifically binds to Annexin IV, post-translational modifications of Annexin IV, or phospholipids
The targeted inhibitor molecule's targeting portion comprises an antibody or fragment thereof that specifically binds to Annexin IV, a post-translational modification found on Annexin IV, or a phospholipid.
Complement inhibitor selection
The complement inhibitor in the targeted molecule is selected from Factor H, DAF, MCP, CD59, Crry, MAp44, and CR1.
Rehabilitation therapy includes cognitive and motor therapy
The rehabilitation therapy provided as part of the method includes at least one therapy selected from cognitive and motor therapy.
The claims cover a method for treating various central nervous system injuries using a composition comprising a targeted inhibitor molecule with specified targeting and inhibitor components, combined with rehabilitation therapies encompassing cognitive and motor therapies.
Stated Advantages
Significantly reduces acute mechanisms of degeneration following stroke, including reduction in infarct volume and improvement in functional recovery.
Allows administration of therapeutic agent even hours after injury, extending the available treatment window compared to current therapies.
Targeted complement inhibition increases bioavailability and efficacy without systemic immunosuppression, reducing risks associated with systemic complement inhibition.
Improves motor recovery, cognitive recovery, and survival when used in combination with rehabilitation therapy or thrombolytic agents such as t-PA.
Documented Applications
Treatment of ischemic stroke to improve survival, reduce hemorrhage, and improve motor and cognitive recovery.
Treatment of traumatic brain injury with improved recovery using targeted complement inhibition.
Treatment of spinal cord injury by administering targeted complement inhibitors in combination with rehabilitation or thrombolytic agents.
Interested in licensing this patent?