Method for achieving desired glial growth factor 2 plasma levels
The present invention relates to administering glial growth factor 2 (GGF2) to a patient in need thereof, to achieve serum levels of GGF2 within a desired therapeutic window determined based on the disease or disorder afflicting the patient. In a particular embodiment, the patient is suffering from a disease or disorder associated with reduced levels of myelination and the GGF2 is administered to promote myelination in the patient.
1. A method for promoting Schwann cell remyelination following administration of glial growth factor 2 (GGF2) in a subject with a disease or disorder associated with reduced levels of myelination, said method comprising providing GGF2 in a pharmaceutically acceptable carrier, wherein the GGF2 is administered in an amount that elicits a plasma level of about 0.001 nM to 0.01 nM GGF2, or wherein the GGF2 is administered in an amount of about 500 ng of GGF2 per kg of body weight;
and administering the GGF2 to the subject.
2. The method of claim 1 , wherein the GGF2 is administered intravenously, intrathecally, or topically.
3. The method of claim 1 , further comprising administering an Mek1/Erk pathway inhibitor.
4. The method of claim 3 , wherein the Mek1/Erk pathway inhibitor is selected from the group consisting of: (3R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-3-[(4-hydroxy-3-methoxyphenyl)methyl]-2-tetrahydrofuranone, (2-(2′-amino-3′-methoxyphenyl)-oxanaphthalen-4-one]), 4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole, 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole, anthra[1,9-cd]pyrazol-6(2H)-one, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene, tipifarnib, sorafenib, TCCCGCCTGTGACATGCATT, 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide, and N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-benzamide.
5. The method of claim 1 , wherein the disease or disorder associated with reduced levels of myelination is selected from the group consisting of: Guillain-Barre Syndrome, chronic inflammatory demyelinating polyneuropathy, peripheral demyelination due to traumatic injury, multiple sclerosis, optic neuritis, central demyelination due to traumatic injury, transverse myelitis, progressive multifocal leukoencephalopathy, Devic's disease (neuromyelitis optica), acute disseminated encephalomyelitis, adrenoleukodystrophy, and adrenoleukoneuropathy.
6. The method of claim 5 , wherein the disease or disorder associated with reduced levels of myelination is multiple sclerosis.
7. The method of claim 5 , wherein the disease or disorder associated with reduced levels of myelination is peripheral demyelination due to traumatic injury.
8. The method of claim 5 , wherein the disease or disorder associated with reduced levels of myelination is central demyelination due to traumatic injury.
9. The method of claim 5 , wherein the disease or disorder associated with reduced levels of myelination is optic neuritis.