Abstract: The invention is based on the introduction of mutations into the amino acid sequence of human Arylsulfatase A (ASA or ARSA) in order to increase protein stability. The invention introduces amino acid mutations, such as deletions, substitutions or additions, into the C-terminal part of the human ARSA enzyme, in particular at a position around or at amino acid 424, which result in a sequence that does not comprise E424. Provided are further nucleic acids and vectors for the expression of the mutated ARSA of the invention, recombinant cells and pharmaceutical composition comprising the mutated ARSA, as well as its use in the treatment of diseases that are characterized by a reduced activity of endogenous ARSA.

Abstract: The present invention pertains to a novel treatment of pathologies caused by an increased synthesis or accumulation of sulfolipids such as sulfatide. The invention provides mutated arylsulfatase A (ARSA or ASA, EC 3.1.6.8) enzymes with increased activity towards sulfatide metabolization. The invention provides nucleic acids encoding the mutant ARSA, the use of the proteins and nucleic acids, as well as pharmaceutical compositions comprising them, in the treatment of lysosomal storage disorders (LSDs) such as metachromatic leukodystrophy (MLD).

Abstract: The present invention pertains to a novel treatment of pathologies caused by an increased synthesis or accumulation of sulfolipids such as sulfatide. The invention provides mutated arylsulfatase A (ARSA or ASA, EC 3.1.6.8) enzymes with increased activity towards sulfatide metabolization. The invention provides nucleic acids encoding the mutant ARSA, the use of the proteins and nucleic acids, as well as pharmaceutical compositions comprising them, in the treatment of lysosomal storage disorders (LSDs) such as metachromatic leukodystrophy (MLD).

Abstract: The present invention pertains to a novel treatment of pathologies caused by an increased synthesis or accumulation of sulfolipids such as sulfatide. The invention provides mutated arylsulfatase A (ARSA or ASA, EC 3.1.6.8) enzymes with increased activity towards sulfatide metabolization. The invention provides nucleic acids encoding the mutant ARSA, the use of the proteins and nucleic acids, as well as pharmaceutical compositions comprising them, in the treatment of lysosomal storage disorders (LSDs) such as metachromatic leukodystrophy (MLD).