Method for treating nervous system injuries using boldine and derivatives thereof
Inventors
Cardozo, Christopher • Toro Chacon, Carlos A. • Graham, Zachary • Zhao, Wei • Saez, Juan C.
Assignees
US Department of Veterans Affairs
Publication Number
US-12246012-B2
Publication Date
2025-03-11
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 include improving voluntary muscle control and treating neuropathic pain in subjects having an injury to the nervous system. The compounds are represented by a specific chemical formula with various substituents, allowing for diverse analogs and derivatives.
The problem being addressed is that injuries to the nervous system, including central nervous system injuries such as spinal cord injuries (SCI) and traumatic brain injuries (TBI), and peripheral nerve injuries, frequently disrupt nerve function and physiological processes. These injuries often result in severe deficits such as paralysis, loss of sensation, and neuropathic pain, which are difficult to treat. While some strides have been made in managing complications, there is no consistent cell-based or pharmacologic approach to improve sensory or motor function after such traumatic injuries. Therefore, there remains a need for effective treatments for nervous system injuries and associated secondary conditions.
Claims Coverage
The patent includes one independent claim directed to a method of improving voluntary muscle control in a subject having an injury to the nervous system, highlighting several inventive features relating to the administered compounds and treatment context.
Use of compounds represented by a specific chemical formula for treatment
The method involves administering an effective amount of a compound represented by a detailed chemical formula comprising various substituents (R1-R7) or their pharmaceutically-acceptable salts to improve voluntary muscle control in a subject with nervous system injury.
Selection of substituents on the compound for effective treatment
Specific selections for substituents are claimed, including R1, R4, and R5 independently selected from hydrogen, methyl, ethyl, and propyl; R2 and R7 independently selected from hydrogen and halogen; and R3 and R6 as hydrogen, with further embodiments where these groups take particular values, enhancing treatment efficacy.
Treatment of various nervous system injuries
The method covers treatment of nervous system injuries including spinal cord injury (SCI), spinal cord contusion, nerve crush injury, and traumatic brain injury (TBI), tailoring the use of the compounds for these injury types.
Addressing neuropathic pain as a symptom
Improving voluntary muscle control further encompasses treating neuropathic pain, a common symptom of nervous system injuries, by administration of the disclosed compounds.
Improvement in locomotor function
The improvement in voluntary muscle control includes enhancing locomotor function, highlighting functional recovery as a key therapeutic goal.
The claims primarily cover administering an effective amount of boldine or its analogs with specified substituents to subjects suffering from nervous system injuries, focusing on improving voluntary muscle control, including locomotor function, and addressing neuropathic pain associated with these injuries.
Stated Advantages
Boldine administration significantly improves locomotor function after spinal cord injury, as evidenced by improved Basso Mouse Scale scores and ladder rung walk test performance in animal models.
Boldine reduces expression of pro-inflammatory cytokines and chemokines linked to pathological pain, such as IL-1β, caspase-1, IL-10, and CCL2, indicating potential anti-inflammatory and neuroprotective effects.
The compounds provide a novel pharmacologic approach to treat nervous system injuries and secondary complications like neuropathic pain, where no consistent treatments currently exist.
Documented Applications
Treatment of injuries to the nervous system in subjects, including central nervous system injuries such as spinal cord injury (SCI), spinal cord contusion, traumatic brain injury (TBI), and peripheral nerve injuries.
Improvement of voluntary muscle control and locomotor function in subjects after nervous system injury.
Treatment of neuropathic pain following nervous system injuries, particularly pain resulting from spinal cord injury or contusion.
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