Glucocorticoid induced leucine zipper mimetics as therapeutic agents in multiple sclerosis
View Patent ↗Polypeptide compositions that mimic the activity of glucocorticoid induced leucine zipper (GILZ) on the immune system are described. Also described is a method of treating multiple sclerosis using compositions comprising GILZ or lower molecular weight polypeptides with structural relationships to GILZ.
1. A pharmaceutical composition comprising a polypeptide from 6 to 35 amino acid residues, the polypeptide comprising 1 to 3 tetrapeptides having the sequence of PXXP, wherein
P is proline; and
X is any amino acid, and
wherein the polypeptide comprises the amino acid sequence of CLSPEEPAPESPQVPEAPGGSAV (SEQ ID NO: 6),
and wherein the pharmaceutical composition further comprises a cell penetrating peptide, wherein the polypeptide and the cell penetrating peptide form a complex.
2. The pharmaceutical composition of claim 1 , wherein at least one tetrapeptide comprises the amino acid sequence of SEQ ID NO: 3.
3. The pharmaceutical composition of claim 1 , wherein at least one tetrapeptide comprises the amino acid sequence of SEQ ID NO: 4.
4. The pharmaceutical composition of claim 1 , wherein at least one tetrapeptide comprises the amino acid sequence of SEQ ID NO: 5.
5. The pharmaceutical composition of claim 1 , wherein the polypeptide comprises a polyproline helical conformation.
6. The pharmaceutical composition of claim 1 , wherein the cell penetrating peptide is Pep-1.
7. The pharmaceutical composition of claim 1 , wherein the composition provides a Th-2 bias in the Th-1/Th-2 balance.
8. A pharmaceutical formulation comprising the pharmaceutical composition of claim 1 .
9. The pharmaceutical formulation of claim 8 further comprising a pharmaceutically acceptable carrier.
10. A lyophilisate or powder of the pharmaceutical formulation of claim 8 .