5-hydroxytryptamine 1B receptor-stimulating agent for use as a promoter of satellite cells self-renewal and/or differentiation
The present invention relates to the field of muscle regeneration, and more particularly to the replenishment of the in vivo muscle stem cells pool. It more specifically relates to a 5-hydroxytryptamine B1 receptor-stimulating agent, and to a composition comprising said agent, for use as i) a promoter of satellite cells self-renewal and/or differentiation, and/or ii) an agent preventing and/or inhibiting the satellite cells pool exhaustion. The invention further encompasses therapeutic and screening methods.
1. A method, comprising:
contacting satellite cells with an effective amount of a direct 5-hydroxytryptamine 1B receptor (5-HT1 BR)-stimulating agent selected from a triptan, a vortioxetine, and an ergotamine, to thereby promote satellite cell proliferation by increasing division rate.
2. The method of claim 1 , wherein the satellite cells are contacted in vitro.
3. The method of claim 2 , wherein the satellite cells are contacted by administering an effective amount of the direct 5-hydroxytryptamine 1B receptor (5-HT1 BR)-stimulating agent to an isolated biological sample comprising satellite cells.
4. The method of claim 1 , wherein the satellite cells are contacted by administering the direct 5-hydroxytryptamine 1B receptor (5-HT1 BR)-stimulating agent to a subject affected by a natural or by a pathological loss and/or damage and/or impairment of skeletal muscle tissue to thereby provide a therapeutic benefit to the subject.
5. The method of claim 4 , wherein the subject has sarcopenia.
6. The method of claim 5 , wherein the subject has cancer-induced sarcopenia.
7. The method of claim 1 , wherein the agent is vortioxetine.
8. The method of claim 1 , wherein the agent is a triptan.
9. The method of claim 8 , wherein the triptan is selected from sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan, naratriptan, avitriptan, and donitriptan.
10. The method of claim 1 , wherein the agent is modified to comprise at least one positively charged chemical moiety.
11. The method of claim 10 , wherein the positively charged chemical moiety is a quaternary ammonium group or a tertiary sulfonium group.
12. The method of claim 10 , wherein the agent is a positively charged vortioxetine selected from the group consisting of salts of vortioxetine, vortioxetine coupled to a positively charged amino acid, pyrrolidinium-vortioxetine, pyperazinium-vortioxetine, dimethylammonium-vortioxetine, sulfonium-vortioxetine, N-oxide-vortioxetine, sulfoxide-vortioxetine, and phosphonium-vortioxetine.
13. The method of claim 10 , wherein the agent is histidine-vortioxetine or pyrrolidinium-vortioxetine.
14. A method of promoting satellite cell proliferation by increasing division rate, comprising administering a pharmaceutical composition comprising at least one direct 5-hydroxytryptamine 1B receptor (5-HT1 BR)-stimulating agent selected from a triptan, a vortioxetine, and an ergotamine and at least one pharmaceutically acceptable excipient to the subject.
15. The method of claim 14 , wherein the agent is vortioxetine.
16. The method of claim 14 , wherein the agent is a triptan.
17. The method of claim 16 , wherein the triptan is selected from sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan, naratriptan, avitriptan, and donitriptan.
18. The method of claim 14 , wherein the agent is modified to comprise at least one positively charged chemical moiety.
19. The method of claim 18 , wherein the positively charged chemical moiety is a quaternary ammonium group or a tertiary sulfonium group.
20. The method of claim 18 , wherein the agent is a positively charged vortioxetine selected from the group consisting of salts of vortioxetine, vortioxetine coupled to a positively charged amino acid, pyrrolidinium-vortioxetine, pyperazinium-vortioxetine, dimethylammonium-vortioxetine, sulfonium-vortioxetine, N-oxide-vortioxetine, sulfoxide-vortioxetine, and phosphonium-vortioxetine.
21. The method of claim 18 , wherein the agent is histidine-vortioxetine or pyrrolidinium-vortioxetine.
22. A method of promoting muscle regeneration and/or delaying progression of at least one of natural or pathological loss, damage and impairment of skeletal muscle in a subject by increasing satellite cell division rate, comprising administering a pharmaceutical composition comprising at least one direct 5-hydroxytryptamine 1B receptor (5-HT1 BR)-stimulating agent selected from a triptan, a vortioxetine, and an ergotamine and at least one pharmaceutically acceptable excipient to the subject.
23. The method of claim 22 , wherein the subject has a pathological loss of skeletal muscle tissue(s).
24. The method of claim 22 , wherein the subject has a natural loss of skeletal muscle tissue(s).
25. The method of claim 22 , wherein the subject has damage and/or impairment of skeletal muscle tissue(s).
26. The method of claim 22 , wherein the subject has sarcopenia.
27. The method of claim 22 , wherein the triptan is selected from sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan, naratriptan, avitriptan, and donitriptan.