Compositions and methods for treating neurodegenerative, myodegenerative, and lysosomal storage disorders
Inventors
Wolf, Christian • KALUVU, Balaraman • Moussa, Charbel
Assignees
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Publication Number
US-12246009-B2
Publication Date
2025-03-11
Expiration Date
Abstract
Provided herein are compositions and methods for treating or preventing a neurodegenerative disease, a myodegenerative disease, a prion disease or a lysosomal storage disease in a subject.
Core Innovation
The patent discloses compounds of a defined Formula I scaffold, including isomers and pharmaceutically acceptable salts. The Formula I scaffold is defined with X as N or CH, Y as aryl or heteroaryl or an N-methylpiperazinyl substituted with R1, and Z as heteroaryl, heterocyclyl, or NR3R4, with R3 and R4 independently selected among H, C1-3 alkyl, C1-3 alkoxy, or unsubstituted phenyl, and n defined as 0-3.
Specific named examples and figures are provided for Formula I derivatives, including morpholinyl (Z) and benzyl substituted with R1 in meta position (Y). The disclosure includes chemically defined thieno[3,2-b]pyridine derivatives and related named compounds such as Compound 1 (BK40197) and Compound 2 (BK40143), among others.
The document frames the compounds in therapeutic context for treatment or prevention of neurodegenerative disease, myodegenerative disease, prion disease, and lysosomal storage disorders. It further describes intended biological effects such as reduced toxic protein aggregation in neuron and enhanced lysosomal clearance, and it identifies toxic proteins and disease-associated proteins including β-amyloid, α-synuclein, tau, and TDP-43.
The document also addresses biological targets and selectivity concepts, including potential receptor tyrosine kinase selectivity such as DDR1 and DDR2, and other receptor tyrosine kinases listed in the disclosure. Extensive experimental sections are described in cell and animal contexts using BK40143/BK40197/BK40196 with tau/α-synuclein models, and the readouts include measures such as cell viability and protein/biomarker assays, along with behavioral testing outcomes.
Claims Coverage
The partial claims set includes four independent claims, covering a defined Formula I compound and three method claims. The inventive features center on the specified Formula I substituent constraints combined with use in treating or preventing disease or inhibiting toxic protein aggregation.
Specified formula i compound with defined substituent constraints
A compound having Formula I, including isomers and pharmaceutically acceptable salts, with X as CH or N, Y as aryl or heteroaryl or an N-methylpiperazinyl substituted with R1, and Z as heteroaryl, heterocyclyl, or NR3R4, with R3 and R4 independently H, C1-3 alkyl, C1-3 alkoxy, or unsubstituted phenyl.
Administering formula i compound to treat or prevent neurodegenerative, myodegenerative, or prion disease
A method of treating or preventing a neurodegenerative disease, a myodegenerative disease, or a prion disease in a subject by administering an effective amount of a Formula I compound or a pharmaceutically acceptable salt.
Contacting a neuron with a formula i compound composition to inhibit or prevent toxic protein aggregation
A method of inhibiting or preventing toxic protein aggregation in a neuron by contacting the neuron with an effective amount of a composition comprising a Formula I compound.
Administering formula i compound to treat or prevent lysosomal storage disease
A method of treating or preventing a lysosomal storage disease in a subject by administering an effective amount of a Formula I compound or a pharmaceutically acceptable salt.
Across the independent claims, coverage is anchored by the Formula I compound definition and its substituent constraints. The methods apply that compound definition to treatment or prevention of neurodegenerative, myodegenerative, prion, and lysosomal storage diseases, and to inhibition or prevention of toxic protein aggregation in neurons.
Stated Advantages
Inhibits or prevents toxic protein aggregation in neurons.
Treats or prevents neurodegenerative diseases, including ALS, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, mild cognitive impairment, α-synucleinopathy, and Tauopathy, as well as myodegenerative diseases and prion diseases.
Treats or prevents lysosomal storage diseases.
Enhanced lysosomal clearance.
Neuroprotective findings including reduced pTau/amyloid and DDR1 deactivation, and effects on α-synuclein.
Documented Applications
Treating or preventing neurodegenerative diseases, including ALS, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, mild cognitive impairment, α-synucleinopathy, and Tauopathy, in a subject having or at risk.
Treating or preventing myodegenerative diseases and prion diseases in a subject having or at risk.
Inhibiting or preventing toxic protein aggregation in a neuron, including aggregation of β-amyloid, α-synuclein, tau, and TDP-43, in vitro and/or in vivo.
Treating or preventing lysosomal storage diseases in a subject.
Combination therapy context that includes administering a second therapeutic agent or therapy together with the Formula I compound.
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