5-hydroxytryptamine 1B receptor-stimulating agent for use as a promoter of satellite cells self-renewal and/or differentiation
View Patent ↗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 in vitro with an effective amount of vortioxetine, or a positively charged vortioxetine that is modified to comprise at least one positively charged chemical moiety, to thereby promote satellite cell self-renewal and/or differentiation.
2. The method of claim 1 , wherein the satellite cells are contacted with the positively charged vortioxetine.
3. The method of claim 1 , wherein the positively charged chemical moiety is a quaternary ammonium group or a tertiary sulfonium group.
4. The method of claim 3 , wherein
the quaternary ammonium group has the formula (I)
—(NR 1 R 2 R 3 ) + Z − (I)
wherein
Z is an organic or inorganic anion; and
R 1 , R 2 and R 3 are each independently selected from the group consisting of alkyl, aryl and cycloalkyl;
or
said tertiary sulfonium group has the formula (II)
—(SR 4 R 5 ) + Z − (II)
wherein
Z is an organic or inorganic anion; and
R 4 and R 5 are each independently selected from the group consisting of alkyl, aryl and cycloalkyl.
5. The method of claim 2 , wherein the positively charged vortioxetine is 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.
6. The method of claim 5 , wherein the positively charged vortioxetine is histidine-vortioxetine or pyrrolidinium-vortioxetine.
7. The method of claim 1 , wherein the satellite cells are contacted with vortioxetine.
8. A method of promoting muscle regeneration in a subject, comprising:
administering vortioxetine, or a positively charged vortioxetine that is modified to comprise at least one positively charged chemical moiety, to a subject in need thereof to thereby promote muscle regeneration in the subject.
9. The method of claim 8 , wherein the subject has a pathological loss of skeletal muscle tissue(s).
10. The method of claim 8 , wherein the subject has a natural loss of skeletal muscle tissue(s).
11. The method of claim 8 , wherein the subject has damage and/or impairment of skeletal muscle tissue(s).
12. The method of claim 8 , wherein the subject has sarcopenia.
13. The method of claim 8 , wherein positively charged vortioxetine is administered to the subject.
14. The method of claim 8 , wherein vortioxetine is administered to the subject.
15. A method of delaying progression of natural or pathological loss and/or damage and/or impairment of skeletal muscle in a subject, comprising:
administering vortioxetine, or a positively charged vortioxetine that is modified to comprise at least one positively charged chemical moiety, to a subject in need thereof to thereby delay progression of natural or pathological loss and/or damage and/or impairment of skeletal muscle in the subject.
16. The method of claim 15 , wherein pathological loss of skeletal muscle tissue in the subject is delayed.
17. The method of claim 15 , wherein natural loss of skeletal muscle tissue in the subject is delayed.
18. The method of claim 15 , wherein damage and/or impairment of skeletal muscle tissue in the subject is delayed.
19. The method of claim 15 , wherein the subject has sarcopenia.
20. The method of claim 15 , wherein positively charged vortioxetine is administered to the subject.
21. The method of claim 15 , wherein vortioxetine is administered to the subject.