US 11,969,522 B2
Use of immune modulators to improve nerve regeneration
Jonathan Cheng, Dallas, TX (US); Edward Keefer, Dallas, TX (US); and Srikanth Vasudevan, Dallas, TX (US)
Assigned to The Board of Regents of the University of Texas System, Austin, TX (US); and Edward Keefer, Dallas, TX (US)
Filed by The Board of Regents of the University of Texas System, Austin, TX (US); and Edward Keefer, Dallas, TX (US)
Filed on Jul. 7, 2020, as Appl. No. 16/922,355.
Claims priority of provisional application 62/871,552, filed on Jul. 8, 2019.
Prior Publication US 2021/0023264 A1, Jan. 28, 2021
Int. Cl. A61L 27/18 (2006.01); A61K 38/18 (2006.01); A61K 45/06 (2006.01); A61K 31/395 (2006.01); A61K 31/5377 (2006.01); C07D 257/02 (2006.01)
CPC A61L 27/18 (2013.01) [A61K 38/18 (2013.01); A61K 38/185 (2013.01); A61K 38/1866 (2013.01); A61K 45/06 (2013.01); A61K 31/395 (2013.01); A61K 31/5377 (2013.01); A61L 2430/32 (2013.01); C07D 257/02 (2013.01)] 21 Claims
 
1. A method of increasing nerve growth, regrowth or regeneration in a subject comprising administering to said subject a CXCR4 antagonist, a STAT3 activator, and/or an agent that increases nitric oxide content, wherein:
(a) the CXCR4 antagonist is selected from the group consisting of Plerixafor, BL-8040, or WZ 811;
(b) the STAT3 activator is selected from the group consisting of colivelin, neuroprotective peptide, ruxolitinib phosphate, a JAK1/JAK2 inhibitor, and IL-6, and
(c) the agent that increases nitric oxide content is selected from the group consisting of (+/−)-S-Nitroso-N-acetylpenicillamine, Molsidomine, 3-Morpholinosydnonimine, Hydroxyguanidine sulfate, Tetrahydrobiopterin (THB) dihydrochloride, S-Nitrosoglutathione (GSNO), Streptozotocin (U-9889), Nicorandil, Dephostatin, DETA NONOate, NOC-12, NOC-18, NOC-5, NOC-7, MAHMA NONOate, PAPA NONOate, Sulfo-NONOate disodium salt, Angeliprimes salt, Diethylamine NONOate, NOR-1, NOR-2, NOR-3, NOR-4, Spermine NONOate, beta-Gal NONOate, BNN3, GEA 3162, GEA 5024, Sodium nitroprusside dihydrate, 10-Nitrooleate, BEC, NO-Indomethacin, Pilotyprimes Acid, SE 175, V-PYRRO/NO, Vinyl-L-NIO Hydrochloride, AMI-1, sodium salt, DAF-FM DA (cell permeable), GEA 5583, N-Acetyl-D,L-penicillamine disulfide, SIN-1A/gammaCD Complex, 4-Phenyl-3-furoxancarbonitrile, JS-K, Lansoprazole Sulfone N-Oxide, NO-Aspirin 1, Glyco-SNAP-2, N,N-Dicarboxymethyl-N,N-dinitroso-p-phenylenediamine (Disodium Salt), (2S)-(+)-Amino-6-iodoacetamidohexanoic acid, 4AF DA, BEC ammonium salt, DAF-2 DA (cell permeable), DAN-1 EE hydrochloride, DD1, DD2, Diethylamine NONOate/AM, Fructose-SNAP-1, Glyco-SNAP-1, Guanylyl Cyclase, Hydroxyguanidine hemisulfate, N-Cyclopropyl-N′-hydroxyguanidine hydrochloride, NOR-5, PROLI NONOate, S-Nitrosocaptopril, 4-(p-methoxyphenyl)-1,3,2-Oxathiazolylium-5-olate, 4-chloro-4-phenyl-1,3,2-Oxathiozolylium-5-olate, 4-phenyl-1,3,2-Oxathiazolylium-5-olate, 4-trifluoro-4-phenyl-1,3,2-Oxathiazolylium-5-olate, Tricarbonyldichloro-ruthenium (II) dimer, DL-alpha-Difluoromethylornithine hydrochloride, Geranylgeranylacetone, N-Nitrosodiethylamine, L-NMMA (citrate), and 3-(Methylnitrosamino)propionitrile, SIN-1 chloride, L-Arginine, SNAP, L-arginine and a PDE5 inhibitor wherein the method results in bridging of a critical gap of at least 3 cm.