Neuroprotective compositions and methods of using the same
Inventors
Erickson, Jeffrey • Wulff, Heike • SHIM, Heesung • Singh, Vikrant • Singh, Latika
Assignees
University of California San Diego UCSD • Louisiana State University
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12661340-B2
Publication Date
2026-06-23
Expiration Date
Abstract
This invention is directed to neuroprotective compositions and methods of using the same to treat neurodegenerative diseases.
Core Innovation
The invention relates to neuroprotective compounds according to specified structures and pharmaceutically acceptable salts thereof. It provides methods for preventing, treating, and/or reducing the severity of neurodegenerative disease by administering a therapeutically effective amount of the neuroprotective compound to a subject in need thereof, and also addresses diseases and conditions associated with glutamate-induced excitotoxicity.
The disclosure presents a series of thiazol-2-amine derivatives, including exemplified compounds such as SKA-41, SKA-75, and SKA-76, and additional derivatives such as SKA190, SKA193, SKA219, SKA247, SKA-375-383, and SKA-384-388. Riluzole and riluzole-derived compounds are described in relation to inhibition of Ca2+-dependent, high-affinity Gln/MeAIB transport, reduced potency against voltage-gated sodium channels, and improved brain penetration, including higher brain/plasma ratio than riluzole.
The invention further proposes that SNAT8 is the mediating transporter for the Gln/MeAIB transport system. It describes approaches directed at reducing CA1 neuronal death and cognitive impairment after global cerebral ischemia by suppressing SNAT8 and administering SKA-41 derivatives, together with discussion of compound selectivity, transporter expression, and experimental endpoints.
Claims Coverage
The provided independent claims comprise methods covering neurodegenerative disease, diseases and conditions associated with glutamate-induced excitotoxicity, and a prophylactic and management strategy to suppress neuronal death and cognitive impairment. Across the independent claims, the core inventive element is administration of a therapeutically effective amount of a neuroprotective compound defined by specified structures and pharmaceutically acceptable salts.
Administering a neuroprotective compound for neurodegenerative disease
A method for preventing, treating, and/or reducing the severity of a neurodegenerative disease by administering to a subject in need thereof a therapeutically effective amount of the neuroprotective compound according to any one of the following structures, and a pharmaceutically acceptable salt thereof.
Targeting glutamate-induced excitotoxicity
A method for preventing, treating, and/or reducing the severity of a disease and/or condition associated with glutamate-induced excitotoxicity by administering to a subject in need thereof a therapeutically effective amount of the neuroprotective compound according to any one of the following structures, and a pharmaceutically acceptable salt thereof.
Suppressing neuronal death and cognitive impairment
A method for effective prophylactic and management strategy to suppress neuronal death and cognitive impairment by administering to a subject in need thereof a therapeutically effective amount of the neuroprotective compound according to any one of the following structures, and a pharmaceutically acceptable salt thereof.
Open-channel NMDA receptor blocker
The method further includes administering, either concurrently or subsequently, a therapeutically effective amount of an open-channel NMDA receptor blocker to the subject, with memantine identified as an example.
The independent claims center on administering a therapeutically effective amount of a neuroprotective compound defined by specified structures and pharmaceutically acceptable salts to prevent, treat, and/or reduce neurodegenerative disease severity, conditions associated with glutamate-induced excitotoxicity, and neuronal death and cognitive impairment. Additional scope includes co- or sequential administration of an open-channel NMDA receptor blocker.
Stated Advantages
Preventing, treating, and/or reducing the severity of a neurodegenerative disease.
Preventing, treating, and/or reducing the severity of a disease and/or condition associated with glutamate-induced excitotoxicity.
Suppressing neuronal death and cognitive impairment through an effective prophylactic and management strategy.
Potently inhibits Ca2+-dependent, high-affinity Gln/MeAIB transport.
Selectively inhibits Gln/MeAIB transport with reduced potency against voltage-gated sodium channels (Nav).
Improved brain penetration, including higher brain/plasma ratio than riluzole.
Reduces CA1 neuronal death after global cerebral ischemia.
Reduces cognitive impairment after global cerebral ischemia.
Documented Applications
Preventing, treating, and/or reducing severity in neurodegenerative diseases including Alzheimer’s disease, global cerebral ischemia, amyotrophic lateral sclerosis, traumatic brain injury-induced epileptogenesis, peri-operative neuronal and/or cardiac stress, epilepsy, noise-induced hearing loss, or combinations thereof.
Managing or preventing cognitive impairment, neurodegeneration, neuronal cell death, excitotoxic cell death, or a combination thereof.
Prevention and reduction of severity of diseases and conditions associated with glutamate-induced excitotoxicity.
Preventing, treating, and/or reducing the severity of a neurodegenerative disease in a subject by administering a neuroprotective compound.
Preventing, treating, and/or reducing the severity of a disease and/or condition associated with glutamate-induced excitotoxicity in a subject by administering a neuroprotective compound.
Providing an effective prophylactic and management strategy to suppress neuronal death and cognitive impairment in a subject by administering a neuroprotective compound.
Interested in licensing this patent?