Compositions and methods for treating inflammatory neurological disorders
Inventors
Huang, Jeffrey • Baydyuk, Maryna
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12447145-B2
Publication Date
2025-10-21
Expiration Date
Abstract
The present application is directed to methods and compositions for treating a condition marked by enhanced inflammation in the central nervous system (CNS). The methods comprise administering to a subject in need of treatment of enhanced inflammation in the CNS an inhibitor of an amino acid transporter in inflammatory cells present in the CNS. The compositions of the present invention relate to compositions comprising an inhibitor of an amino acid transporter in inflammatory cells, or a pharmaceutically acceptable salt thereof, wherein the composition is formulated for direct administration into the CNS of a mammal.
Core Innovation
The document describes a method of promoting remyelination of neurons in the central nervous system (CNS) in a condition marked by enhanced inflammation in the CNS and demyelination of neurons in a subject. The method includes administering an inhibitor of large amino acid transporter small subunit 1 (LAT1) protein, and the inhibitor is described as inhibiting LAT1 protein in microglia, macrophages, B-cells, or a combination thereof, present in the CNS.
The core approach centers on inhibiting LAT1 in CNS inflammatory cells, including microglia and optionally other inflammatory cells such as macrophages and T- and B-cells. The document further emphasizes direct administration into the CNS and uses LAT1 (Slc7a5) as a target associated with enhanced and unresolved inflammation. It links the presence of CNS inflammation to remyelination failure, including in progressive multiple sclerosis, and frames LAT1 inhibition as a way to address demyelination-related inflammatory pathology.
The document provides experimental and mechanistic support using Slc7a5 mRNA expression increasing in lesions and co-localization with CD3+ T cells and CX3CR1+ microglia/macrophages. It describes JPH203 (and JPH203 hydrochloride) as an example inhibitor and reports improved motor recovery and prophylactic prevention of progression in experimental autoimmune encephalomyelitis, and increased mature oligodendrocytes with reduced pro-inflammatory iNOS+ microglia/macrophage inflammation in lysolecithin demyelination.
Claims Coverage
One independent claim is provided. The inventive features collectively cover promoting remyelination in a CNS condition with enhanced inflammation and demyelination by administering a LAT1 protein inhibitor that inhibits LAT1 in specified CNS inflammatory cell populations.
Promoting remyelination in enhanced-inflammation CNS demyelination conditions by administering a LAT1 protein inhibitor
Administering to the subject an inhibitor of large amino acid transporter small subunit 1 (LAT1) protein to promote remyelination of neurons in the CNS in a condition marked by enhanced inflammation in the CNS and demyelination of neurons.
Inhibiting LAT1 in specific CNS inflammatory cell populations
The inhibitor inhibits LAT1 protein in microglia, macrophages, B-cells, or a combination thereof, present in the CNS.
The independent claim coverage focuses on remyelination promotion in an enhanced-inflammation demyelinating CNS condition by LAT1 protein inhibition, with LAT1 inhibition specifically directed to microglia, macrophages, B-cells, or combinations present in the CNS.
Stated Advantages
Improves motor recovery in experimental autoimmune encephalomyelitis.
Prevents progression in a prophylactic setting in experimental autoimmune encephalomyelitis.
Increases mature oligodendrocytes in lysolecithin demyelination.
Reduces pro-inflammatory iNOS+ microglia/macrophage inflammation in lysolecithin demyelination.
Promotes OPC differentiation and remyelination.
Reduces neuronal degeneration.
Documented Applications
Treating or addressing progressive demyelination associated with CNS enhanced/unresolved inflammation, including in progressive multiple sclerosis.
Treating multiple sclerosis, including primary progressive MS (PPMS) and secondary progressive MS (SPMS), as described in the document.
Treating neuromyelitis optica (NMO) and NMOSD, as described in the document.
Treating autoimmune encephalitis, as described in the document.
Treating acute disseminated encephalomyelitis (ADEM), as described in the document.
Treating traumatic brain injury (TBI), as described in the document.
Treating stroke, as described in the document.
Experimental use in experimental autoimmune encephalomyelitis (EAE).
Experimental use in lysolecithin demyelination (focal demyelination).
Interested in licensing this patent?