Methods for promoting myelination, neuronal survival and oligodendrocyte differentiation via administration of Sp35 or TrkA antagonists
View Patent ↗This invention relates to methods for promoting myelination, neuronal survival, and oligodendrocyte differentiation and treating demyelination and dysmyelination disease by the administration of a TrkA antagonist. The invention also relates to methods of inhibiting or decreasing Sp35 expression by the use of a TrkA antagonist. Additionally, the invention relates generally to methods for blocking Sp35 and TrkA interaction and inhibiting or decreasing TrkA phosphorylation by the administration of a Sp35 antagonist.
1. A method for promoting myelination of central nervous system (CNS) neurons, comprising contacting a mixture of CNS neurons and oligodendrocytes with a composition comprising a TrkA antagonist consisting of residues 36-441 of SEQ ID NO: 4 or residues 1-441 of SEQ ID NO: 4.
2. The method of claim 1 , wherein said TrkA antagonist polypeptide further comprises a non-TrkA moiety.
3. The method of claim 2 , wherein said non-TrkA moiety is selected from the group consisting of an antibody Ig moiety, a serum albumin moiety, a targeting moiety, a reporter moiety, and a purification-facilitating moiety.
4. The method of claim 1 , wherein said TrkA antagonist polypeptide is conjugated to a polymer.
5. The method of claim 4 , wherein the polymer is a polyalkylene glycol.
6. A method for promoting survival of CNS neurons in a mammal, comprising administering to a mammal in need thereof an effective amount of a composition comprising a TrkA antagonist consisting of residues 36-441 of SEQ ID NO: 4 or residues 1-441 of SEQ ID NO: 4.
7. The method of claim 6 , wherein said CNS neurons and oligodendrocytes are in a mammal and said mammal has been diagnosed with a disease, disorder, or injury involving demyelination, dysmyelination, or neurodegeneration.
8. The method of claim 7 , wherein said disease, disorder, or injury is selected from the group consisting of multiple sclerosis (MS), progressive multifocal leukoencephalopathy (PML), encephalomyelitis (EPL), central pontine myelolysis (CPM), adrenoleukodystrophy, Alexander's disease, Pelizaeus Merzbacher disease (PMZ), Wallerian Degeneration, optic neuritis, transverse myelitis, amylotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, spinal cord injury, traumatic brain injury, post radiation injury, neurologic complications of chemotherapy, stroke, acute ischemic optic neuropathy, vitamin E deficiency, isolated vitamin E deficiency syndrome, AR, Bassen-Kornzweig syndrome, Marchiafava-Bignami syndrome, metachromatic leukodystrophy, trigeminal neuralgia, acute dissmeminated encephalitis, Guillian-Barre syndrome, Marie-Charcot-Tooth disease and Bell's palsy.
9. A method for inhibiting Sp35 expression in CNS neurons comprising contacting CNS neurons with a composition comprising a TrkA antagonist consisting of residues 36-441 of SEQ ID NO: 4 or residues 1-441 of SEQ ID NO: 4.
10. The method of claim 9 , wherein said CNS neurons are in a mammal, and wherein said contacting comprises administering an effective amount of said TrkA antagonist to a mammal in need thereof.