Therapy for Transthyretin-Associated Amyloidosis

A catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with an additional therapeutic agent selected from the group consisting of another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline and epigallocatechin-3-gallate, wherein the benzoxazole derivative is a compound of formula V

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is COOR, tetrazolyl, CONHOR, B(OH)2 or OR;
• X is 0;
• and
• R1, R2 and R3 are each independently selected from hydrogen, halo, OR, B(OH)2 or CF3, and wherein
• R is hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 cycloalkyl, C1-C6 heterocyclyl, phenyl, xylyl, naphthyl, thienyl, indolyl or pyridyl.

A combination of a catechol-O-methyltransferase (COMT) inhibitor and an additional therapeutic agent selected from the group consisting of another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline and epigallocatechin-3-gallate, for use in the prevention and/or treatment of transthyretin-associated amyloidosis, wherein the benzoxazole derivative is a compound of formula V

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is COOR, tetrazolyl, CONHOR, B(OH)2 or OR;
• X is 0;
• and
• R1, R2 and R3 are each independently selected from hydrogen, halo, OR, B(OH)2 or CF3, and wherein
• R is hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 cycloalkyl, C1-C6 heterocyclyl, phenyl, xylyl, naphthyl, thienyl, indolyl or pyridyl.

A therapeutic agent selected from the group consisting of a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline and epigallocatechin-3-gallate, for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with a catechol-O-methyltransferase (COMT) inhibitor, wherein the benzoxazole derivative is a compound of formula V

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is COOR, tetrazolyl, CONHOR, B(OH)2 or OR;
• X is 0;
• and
• R1, R2 and R3 are each independently selected from hydrogen, halo, OR, B(OH)2 or CF3, and wherein
• R is hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 cycloalkyl, C1-C6 heterocyclyl, phenyl, xylyl, naphthyl, thienyl, indolyl or pyridyl.