Patent ID: 6974798

Claim:
A pharmaceutical composition, comprising a pharmaceutical agent capable of ototoxin-induced balance impairment and a trkB or trkC agonist in an amount therapeutically effective for treating ototoxicity caused by the pharmaceutical agent, wherein said agonist is (a) a NT-4/5 (SEQ ID NO:1) variant comprising one to five amino acid alterations selected from the group consisting of: G78-->K, H, Q or R, R85-->E, F, P, Y or W, a conservative amino acid substitution at any of positions R11, G12, E13, V16, D18, W23, V24, D26, V40, L41, Q54, Y55, F56, E58, T59, G77, R79, G80, H85, W86, A99, L100, T101, W110, R111, W112, I113, R114, I115, D116, and T118, 65NAE67→NAS or NAT, ΔC78, ΔC61, ΔQ54-ΔT59, ΔR60-ΔD82, ΔH85-ΔS88, ΔW86-ΔT101, R53→H, K91→H, V108→F, R84→Q, H, N, T, Y or W, D116→E, N, Q, Y, S, or T, wherein Δ indicates deletion of a single amino acid or deletion of the indicated span of residues, inclusive; or (b) a NT-4/5 (SEQ ID NO:1) fragment selected from the group consisting of NT-4/5(R83-Q94), NT-4/5(G1-C61), NT-4/5(G1-C17), NT-4/5(C17-C61), NT-4/5(C17-C78), NT-4/5(C17-C90), NT-4/5(C17-C119), NT-4/5(C17-C121), NT-4/5(R11-R27), NT-4/5(R11-R34), NT-4/5(R34-R53), NT-4/5(C61-C78), NT-4/5(R53-C61), NT-4/5(C61-C119), NT-4/5(C61-C78), NT-4/5(C78-C119), NT-4/5(C61-C90), NT-4/5(R60-C78), NT-4/5(K62-C119), NT-4/5(K62-K91), NT-4/5(R79-R98), NT-4/5(R83-R93), NT-4/5(T101-R111), NT-4/5(G1-C121)VLTVKRVRR (SEQ ID NO:4), NT-4/5(V40-C121)VLTVKRVRR (SEQ ID NO:5), NT-4/5(V40-C121)SLTIKRIRA (SEQ ID NO:6), NT-4/5(V40-C121) TLSRKAGRRA (SEQ ID NO:7), DDDSPIARRGEISVCDSVSDWVSAPDKDTAVDIKGDDVMVLKKVGINHSV (SEQ ID NO:8), and NT-4/5(V40-C121).