A METHOD FOR THE TREATMENT OF POMPE DISEASE USING 1- DEOXYNOJIRIMYCIN DERIVATIVES

摘要

A combination therapy for use in the treatment of Pompe Disease, the combination therapy comprising a 1-deoxynojirimycin (DNJ) derivative and acid ±-glucosidase (Gaa), wherein the DNJ derivative comprises a compound of the formula: where R 1 is H or a straight or branched alkyl, cycloalkyl, alkenyl, alkoxyalkyl or aminoalkyl containing 1-12 carbon atoms, an aryl, alkylaryl, heteroaryl, or heteroaryl alkyl containing 5-12 ring atoms, where R 1 is optionally substituted with one or more -OH, -COOH, -Cl, -F, -CF 3 ,-OCF 3 , -O-C(=O)N-(alkyl) 2 ; R 2 is H; a straight or branched alkyl, cycloalkyl, alkenyl, alkylaryl, or alkoxyalkyl, containing 1 - 9 carbon atoms or aryl containing 5 - 12 carbon atoms, wherein R 2 is optionally substituted with -OH, -COOH, -CF 3 , -OCF 3 or a heterocyclic ring; and at least one of R 1 and R 2 is not H; or a pharmaceutically acceptable salt thereof, wherein the DNJ derivative is used for increasing the activity of Gaa enzyme in a cell, at a concentration at or below the IC 50 value for inhibition of intestinal Gaa; and wherein the DNJ derivative is not 1-deoxynojirimycin or ±-homonojirimycin.