Materials and methods for treating disorders associated with sulfatase enzymes

Abstract

The subject invention concerns materials and methods for treating or preventing disease and conditions associated with various sulfatase enzymes that are defective or that are not properly expressed in a person or animal. In one embodiment, the disease is Sanfilippo A (MPS-IIIA) disease. The subject invention also concerns materials and methods for treating or preventing multiple sulfatase deficiency (MSD) in a person or animal. Compounds of the invention include a fusion protein comprising i) a mammalian sulfatase, or an enzymatically active fragment or variant thereof, and ii) a plant lectin or a binding subunit thereof. In a specific embodiment, the mammalian sulfatase is a human sulfatase, or an enzymatically active fragment or variant thereof. Polynucleotides encoding the fusion proteins are also contemplated for the subject invention. The subject invention also concerns materials and methods for producing proteins of the invention.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]The present application claims the benefit of U.S. Provisional Application Ser. No. 62 / 023,571, filed Jul. 11, 2014, which is hereby incorporated by reference herein in its entirety, including any figures, tables, nucleic acid sequences, amino acid sequences, or drawings.BACKGROUND OF THE INVENTION[0002]There is a need in the art for an effective enzyme replacement therapy (ERT) for patients having disorders associated with sulfatase enzymes. For example, Sanfilippo A (mucopolysaccharidosis IIIA; MPS-IIIA) is a rare genetic lysosomal storage disorder (LSD) affecting about 1 in 150,000 births, with prevalence as high as 1 / 24,000 in some regions. MPS-IIIA is caused by a genetic defect in the gene for the lysosomal enzyme heparan N-sulfatase (N-sulfoglucosamine sulfohydrolase; SGSH) and is characterized by relatively mild somatic features but severe neurological manifestations (decline of learning abilities, hyperactivity, behavior problems, ...

AI Technical Summary

Benefits of technology

The patent is about using plants to make materials that can treat or prevent diseases associated with a lack of certain proteins in humans or animals. One disease that can be treated is Sanfilippo A disease, and the invention also covers methods to treat multiple sulfatase deficiency. The use of plants and a new expression system make the process faster and more flexible, which makes it easier to target rare diseases and disorders of the lysosomal stage.

Problems solved by technology

MPS-IIIA is caused by a genetic defect in the gene for the lysosomal enzyme heparan N-sulfatase (N-sulfoglucosamine sulfohydrolase; SGSH) and is characterized by relatively mild somatic features but severe neurological manifestations (decline of learning abilities, hyperactivity, behavior problems, sleep difficulties, seizures) leading to dementia and death during puberty or early adulthood.

Currently treatment options are limited to symptom management and development of an effective ERT drug has been hindered by the challenges of severe central nervous system (CNS) involvement in this disease.

In lysosomal ERT development, the targeting of drug delivery to disease susceptible organs, tissues, cells, and intracellular lysosomes remains challenging.

Of the ERTs commercially available for lysosomal disorders, none address neurological pathologies of these diseases.

Nevertheless, since plants do not possess the class of mammalian sulfatase related enzymes described in this patent specification, it was not obvious that active forms of these proteins could be successfully expressed in plants.

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