Method for treating nervous system injuries using boldine and analogs thereof
Inventors
Cardozo, Christopher • Toro Chacon, Carlos A. • Graham, Zachary • Zhao, Wei • Saez, Juan C.
Assignees
US Department of Veterans Affairs
Publication Number
US-11707459-B2
Publication Date
2023-07-25
Expiration Date
2041-02-08
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Abstract
Provided are methods of treating an injury to the nervous system in a subject comprising administering to the subject an effective amount of boldine, a boldine analog, or a pharmaceutically-acceptable salt thereof. Also provided are methods of improving voluntary muscle control and methods of treating neuropathic pain in a subject having an injury to the nervous system. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
Core Innovation
The invention provides methods of treating an injury to the nervous system in a subject by administering an effective amount of boldine, a boldine analog, or a pharmaceutically-acceptable salt thereof. The methods also include improving voluntary muscle control and treating neuropathic pain in subjects having nervous system injuries through administration of these compounds represented by a specified chemical formula with various substituent options.
The problem being solved arises from the frequent disruption of nerve function due to injuries to the nervous system, which interfere with physiological processes controlled by nerves. Injuries such as spinal cord injury (SCI), traumatic brain injury (TBI), or peripheral nerve injuries often result in paralysis, loss of sensation, dysregulation of autonomic function, and neuropathic pain that is difficult to treat with conventional medications. Despite advances in addressing complications of nervous system injuries, there remains no consistent pharmacologic approach to improving sensory or motor function after traumatic nerve injury, highlighting a need for effective treatments that also address secondary conditions such as neuropathic pain.
Claims Coverage
The patent includes two independent claims covering methods of treating spinal cord injury using compounds represented by a specific structural formula and administering an effective amount of such compounds.
Method of treating spinal cord injury by administering a compound
A method comprising administering to a subject an effective amount of a compound of the specified structural formula or its pharmaceutically-acceptable salt, wherein the compound has defined substituents. The administration can be oral or intravenous, and can be given up to 24 hours after spinal cord injury.
Intravenous administration of a specific compound for treating spinal cord injury
A method based on intravenously administering to a subject an effective amount of a compound having a specified structure per the formula detailed in the patent, to treat spinal cord injury.
The claims focus on the therapeutic use of compounds represented by a detailed structural formula, particularly boldine or analogs thereof, for treating spinal cord injury by administering effective amounts, including methods of oral or intravenous administration shortly after injury.
Stated Advantages
Administration of boldine significantly improves locomotor function after spinal cord injury as evidenced by behavioral tests in mice.
Boldine reduces neuropathic pain following spinal cord injury through reductions in pro-inflammatory cytokine and chemokine expression in brain and spinal cord tissues.
The compound normalizes injury-induced elevation of inflammatory markers such as IL-1β and CCL2 in affected brain regions.
Documented Applications
Treatment of nervous system injuries including spinal cord injury, spinal cord contusion, nerve crush injury, and traumatic brain injury.
Improvement of voluntary muscle control and locomotor function in subjects having nervous system injuries.
Treatment of neuropathic pain resulting from traumatic injuries to the central or peripheral nervous system.
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