Use of semaphorin 6A for promoting myelination and oligodendrocyte differentiation
View Patent ↗The invention provides methods of treating diseases, disorsers or injuries involving demyelination and dysmyelination, including multiple sclerosis, by the administration of a Sema6A polypeptide.
1. A method for promoting proliferation, differentiation, or survival of oligodendrocytes to a mammal in need thereof, comprising administering to the mammal an effective amount of a composition comprising an isolated mammalian semaphorin 6A (“Sema6A”) polypeptide, which comprises amino acids 56 to 472 of SEQ ID NO: 2, wherein the administering is via intraocular, intrathecal, subdural, intracerebroventricular, intracranial or intralesional administration or is an administration directly into the central nervous system and wherein the administering promotes proliferation, differentiation, or survival of oligodendrocytes to the mammal.
2. A method for promoting oligodendrocyte-mediated myelination of neurons to a mammal in need thereof, comprising administering to the mammal an effective amount of a composition comprising an isolated mammalian Sema6A polypeptide, which comprises amino acids 56 to 472 of SEQ ID NO: 2, wherein the administering is via intraocular, intrathecal, subdural, intracerebroventricular, intracranial or intralesional administration or is an administration directly into the central nervous system and wherein the administering promotes oligodendrocyte-mediated myelination of neurons to the mammal.
3. The method of claim 1 or 2 , wherein the administering treats a disease, disorder, or injury associated with dysmyelination or demyelination or destruction of myelin in said mammal.
4. The method of claim 1 or 2 , wherein the administering treats a disease, disorder, or injury associated with oligodendrocyte death or lack of differentiation in said mammal.
5. The method of claim 1 or 2 , wherein said Sema6A polypeptide binds to a plexin-A2 polypeptide.
6. The method of claim 5 , wherein said Sema6A polypeptide is attached to a non-Sema6A moiety.
7. The method of claim 3 , 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, Bassen-Kornzweig syndrome, Marchiafava-Bignami syndrome, metachromatic leukodystrophy, trigeminal neuralgia, and Bell's palsy.
8. The method of claim 3 , wherein said disease, disorder, or injury is multiple sclerosis (MS).
9. The method of claim 6 , wherein the non-Sema6A moiety is a heterologous polypeptide selected from c-myc, human placental alkaline phosphatase, an immunoglobulin hinge and Fc region and a combination of two or more of the heterologous polypeptides.
10. The method of claim 9 , wherein the non-Sema6A moiety is a polymer.
11. The method of claim 1 or 2 , wherein the composition is administered directly into the central nervous system.
12. The method of claim 1 or 2 , wherein the isolated Sema6A polypeptide comprises, consists essentially of, or consists of an extracellular domain.
13. An in vitro method for promoting proliferation, differentiation, or survival of oligodendrocytes or oligodendrocyte-mediated myelination of neurons, comprising contacting the oligodendrocytes or a mixture of neurons and oligodendrocytes with an effective amount of a composition comprising an isolated Sema6A polypeptide, which comprises amino acids 56 to 472 of SEQ ID NO: 2.
14. The method of claim 13 , wherein the Sema6A polypeptide binds to a plexin-A2 polypeptide.