Treatment of obesity and obesity related disorders by pharmalogical targeting of Kv1.3 potassium channels
Activation of brown adipose tissue, treatment of obesity and/or treatment of obesity-related disorders in human or non-human animal subjects by administering to the subject a potassium channel inhibiting agent. The potassium channel inhibiting agent may comprise ShK toxin or a modified ShK toxin. Examples of modified ShK toxins include ShK-186.
1. A method for activation of brown adipose tissue in a human or animal subject, said method comprising the steps of administering to a subject in need of treatment for hyperphagia, hyperlipidemia, dyslipidemia, hyperglycemia, or hypercholesteremia, an agent which inhibits potassium channels, wherein the agent comprises an ShK toxin attached to a chemical entity, wherein the chemical entity attached to the Shk toxin is selected from: AEEAc-L-Tyr(PO3H2), AEEAc-L-Pmp(OH2), AEEAc-D-Pmp(OH2), AEEAc-D-Pmp(OH, Et), AEEAc-L-Pmp(Et2), AEEAc-D-Pmp(Et2), AEEAc-L-Tyr, AEEAc-L-Phe(p-NH2), AEEAc-L-Phe(p-CO2H), AEEAc-L-Aspartate, AEEAc-D-Aspartate, AEEAc-L-Glutamate, and AEEAc-D-Glutamate.
2. The method according to claim 1 wherein the agent comprises the ShK toxin of SEQ ID NO:1.
3. The method according to claim 1 wherein the agent comprises the Shk toxin selected from: SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 or SEQ ID NO:7.
4. The method according to claim 1 wherein said chemical entity is attached to the N-terminal residue of ShK.
5. The method according to claim 1 wherein the ShK toxin is obtained from a natural source.
6. The method according to claim 1 wherein the ShK toxin is synthetic.
7. The method according to claim 1 wherein the chemical entity includes a fluorophore tag.
8. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Pmp(OH2).
9. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-D-Pmp(OH2).
10. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-D-Pmp(OH, Et).
11. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Pmp(Et2).
12. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-D-Pmp(Et2).
13. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Tyr.
14. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Phe(p-NH2).
15. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Phe(p-CO2H).
16. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Aspartate.
17. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-D-Aspartate.
18. The method according to claim 1 wherein the chemical entity attached to ShK toxin comprises AEEAc-L-Glutamate.
19. The method of claim 1 , wherein the agent is administered at a dose of about 0.001 to about 1000 μg/kg body weight per day.
20. The method of claim 19 , wherein the agent is administered at a dose of about 0.001 to about 500 μg/kg body weight per day.