Patent ID: 7012063
Filing Date: 2006-03-14
Classification: A61K

Abstract:
1. A method of reducing degeneration of an axon predetermined to be subject to degenerative neuropathy in a term patient, the method comprising: contacting the axon in situ with an effective amount of a ubiquitin-proteasome system (UPS) inhibitor sufficient to reduce degeneration of the axon; and detecting a resultant reduction in the degeneration of the axon in situ, wherein the inhibitor is a proteasome inhibitor selected from the group consisting of: MG-132 (Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal), MG-115 (Carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal), PSI(Carbobenzoxy-L-isoleucyl-γ-t-butyl-L-glutamyl-L-alanyl-L-leucinal), Lactacystin (Synthetic: N-Acetyl-L-Cysteine, S-[2R,3 S,4R]-3-Hydroxy-2-[(1S)-1-Hydroxy-2-Methylpropyl]-4-Methyl-5-Oxo-2-Pyrolidinecarbonyl]), PS-519 (clasto-Lactacystin β-Lactone), α-Methylomuralide(α-Methyl clasto-Lactacystin β-Lactone), MG-101 (Ac-Leu-Leu-Nle-CHO), MG-262 (Z-Leu-Leu-Leu-B(OH)2), PS-341 (Velcade; bortezomib), and Epoxomicin ((2R)-2-[Acetyl-(N-Methyl-L-Isoleucyl)-L-Isoleucyl-L-Threonyl-L-Leucyl]-2-Methyloxirane), wherein the degenerative neuropathy is axon trauma or axotomy, and wherein the contacting is effected by local, regionally-restricted delivery of the inhibitor proximate to the axon.