Compounds for intracellular delivery of therapeutic moieties to nerve cells
A compound for delivering a non-cytotoxic therapeutic moiety into nerve cells, the compound having the general formula: B-L-TM where: B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; TM is a therapeutic moiety which has a non-cytotoxic therapeutic effect when absorbed by a nerve cell; and L is a linker coupling B to TM.
1. A composition comprising:
a compound having the general formula:
B-L-M
where:
B is brain derived neurotrophic factor (BDNF) or a fragment thereof which selectively binds to a neurotrophin receptor;
M is a steroid; and
L is a linker coupling B to M; and
a pharmaceutically acceptable vehicle.
2. The composition of claim 1 , wherein B is a BDNF fragment capable of binding TrkB and triggering absorption of the compound.
3. The composition of claim 1 , wherein the linker is a cleavable linker.
4. The composition of claim 1 , wherein the linker L is an amide, alkylamine, thioether, alkyl, cycloalkyl, or aryl linker.
5. The composition of claim 1 , wherein the linker is selected from a chemically cleavable linker, an acid-labile linker, a linker cleavable by hydrolysis, or a linker cleavable by reduction of a disulfide bond.
6. The composition of claim 1 , wherein the steroid is a corticosteroid.
7. The composition of claim 1 , wherein the steroid is cortisone.
8. The composition of claim 1 , wherein the steroid is progesterone.
9. The composition of claim 1 , wherein the steroid is estrogen.
10. The composition of claim 1 , wherein the linker is an amide linker.
11. The composition of claim 1 , wherein said linker is an alkylamine linker.
12. The composition of claim 1 , wherein said linker is a thioether linker.
13. The composition of claim 1 , wherein said linker is an alkyl linker.
14. The composition of claim 1 , wherein said linker is a cycloalkyl linker.
15. The composition of claim 1 , wherein said linker is an aryl linker.
16. The composition of claim 1 , wherein said linker is a linker cleavable by reduction of a disulfide bond.
17. The composition of claim 1 , wherein said linker is an acid labile linker.
18. A method for delivering a steroid selectively into a nerve cell, the method comprising:
administering the compound of claim 1 to the nerve cell,
wherein binding of B to the neurotrophin receptor triggers absorption of the receptor-bound compound and delivery of the steroid into the nerve cell.
19. The method of claim 18 , wherein the nerve cell is infected with a virus.
20. The method of claim 18 , wherein the nerve cell is a damaged nerve cell.