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 of inhibiting Mek1/Erk1 activation for avoiding inhibition of Schwann cell myelination following administration of a polypeptide comprising epidermal growth factor like (EGFL) domain of glial growth factor 2 (GGF2), in a subject, said method comprising:
administering an amount of the polypeptide to the subject sufficient to elicit a plasma level of between about 0.0005 and about 0.01 nM of the polypeptide.
2. The method of claim 1 , wherein the polypeptide is administered intravenously, intrathecally, or topically.
3. The method of claim 1 , wherein the elicited plasma level is of about 0.01 nM of the polypeptide.
4. The method of claim 1 , wherein the amount of the polypeptide is about 500 ng per kg of body weight.
5. The method of method of claim 1 , wherein the elicited plasma level is about 0.0005 nM of the polypeptide.
6. The method of method of claim 1 , wherein the elicited plasma level is about 0.001 nM of the polypeptide.
7. The method of method of claim 1 , wherein the elicited plasma level is about 0.003 nM of the polypeptide.
8. The method claim 1 , further comprising administering an amount of a Mek1/Erk pathway inhibitor to the patient in an amount sufficient to inhibit the Mek1/Erk pathway.
9. The method of claim 8 , 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.