Mutated Arylsulfatase A

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This patent discloses mutated versions of the human arylsulfatase A (ARSA) enzyme, specifically engineered to have significantly higher activity in breaking down sulfatides. Since the lack of functional ARSA leads to the accumulation of sulfatides and consequent lysosomal storage disorders like metachromatic leukodystrophy (MLD), these enhanced enzymes or their genetic codes can be used in pharmaceutical compositions, gene therapy, or enzyme replacement therapy to more effectively treat affected patients.

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• Treatment of metachromatic leukodystrophy (MLD) through enzyme replacement therapy (ERT) using the mutated ARSA enzyme.
• Gene therapy approaches for lysosomal storage disorders (LSDs) by introducing nucleic acids encoding the improved ARSA into patient cells or stem cells.
• Production of pharmaceutical compositions containing the mutated ARSA for intravenous, intrathecal, or intracerebroventricular administration.
• Creation of recombinant cells (e.g., CHO or hematopoietic stem cells) expressing mutated ARSA for drug production or cell therapy.
• Potential treatment of other demyelinating disorders or leukodystrophies characterized by ARSA deficiency and sulfatide accumulation.

BenefitsContent extracted from patent full text and abstract with AI.

• Mutated ARSA enzyme variants demonstrate up to fivefold increased catalytic activity compared to the wild-type human enzyme, enabling more efficient sulfatide breakdown at lower concentrations.
• Improved efficacy in treating MLD and related disorders, possibly with lower dosage requirements, reducing risk and cost associated with high-dose enzyme therapies.
• Greater likelihood of overcoming central nervous system barriers since more active enzyme or gene products can be used in gene and enzyme replacement therapy.
• Reduced risk of immune response and adverse events due to lower required dosing for therapeutic effect.
• Enables both enzyme replacement and gene therapy options, giving flexibility for different clinical situations and patient needs.

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Inventors & Applicants

Patent 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).