Compositions and methods for increasing remyelination
OwnerBradley TAIT, Michael R. JIROUSEK +2inventors
InventorsBradley TAIT, Michael R. JIROUSEK, Christopher LOOSE, William W. CHIN
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Abstract
Provided are compositions and methods comprising a MAChR antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist for increasing proliferation Oligodendrocyte Progenitor Cells (OPCs) into mature, myelinating oligodendrocytes, and related methods of treating demyelination disorders.
Claims62
A method of increasing oligodendrocyte precursor cell (OPC) differentiation, comprising contacting an OPC with:
- (a) an agent having dual activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist;
- or
- (b) a first agent having activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a second agent having activity as a histamine H3 receptor antagonist/inverse agonist/partial agonist, wherein the OPC is contacted with the first agent and second agent in any order or simultaneously,
- thereby increasing OPC differentiation compared to a vehicle control.
A method of producing an expanded population of oligodendrocytes, comprising contacting an oligodendrocyte precursor cell (OPC) with
- (a) an agent having dual activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist;
- or
- (b) a first agent having activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a second agent having activity as a histamine H3 receptor antagonist/inverse agonist/partial agonist, wherein the OPC is contacted with the first agent and second agent in any order or simultaneously,
- thereby producing an expanded population of oligodendrocytes compared to a vehicle control.
A method of increasing remyelination in a subject in need thereof, comprising administering to the subject:
- (a) an agent having dual activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist;
- or
- (b) a first agent having activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a second agent having activity as a histamine H3 receptor antagonist/inverse agonist/partial wherein administration of the first agent and second agent can occur in any order or simultaneously,
- wherein administration of the agent(s) of (a) or (b) increases remyelination in the subject.
A method of treating a demyelination disease or disorder in a subject in need thereof, comprising administering to the subject:
- (a) an agent having dual activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist;
- or
- (b) a first agent having activity as muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a second agent having activity as a histamine H3 receptor antagonist/inverse agonist/partial agonist wherein administration of the first agent and second agent can occur in any order or simultaneously,
- wherein administration of the agent(s) of (a) or (b) increases remyelination and/or reduces a sign or symptom of the disease or disorder in the subject.
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9-15. (canceled)
17-52. (canceled)
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73-74. (canceled)
A pharmaceutical composition, comprising a pharmaceutically-acceptable carrier, and
- a) an agent having dual activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist;
- or
- (b) a first agent having activity as a muscarinic acetylcholine receptor (MAChR) antagonist/inverse agonist/partial agonist and a second agent having activity as a histamine H3 receptor antagonist/inverse agonist/partial agonist.
88-92. (canceled)
94-129. (canceled)
A container comprising a MAChR antagonist/inverse agonist/partial agonist and instructions, where those instructions describe the MAChR antagonist/inverse agonist/partial agonist use in treating or preventing a demyelinating disorder in a subject, wherein the instructions require that the subject has been, or will be, administered MAChR antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist.
A container comprising a histamine H3 receptor antagonist/inverse agonist/partial agonist and instructions, where those instructions describe the a histamine H3 receptor antagonist/inverse agonist/partial agonist use in treating or preventing a demyelinating disorder in a subject, wherein the instructions require that the subject has been, or will be, administered MAChR antagonist/inverse agonist/partial agonist and a histamine H3 receptor antagonist/inverse agonist/partial agonist.
Dependencies are inferred from the claim text.