Compositions and methods for treating lysosomal storage disease

Abstract

The present invention provides recombinant viral and non-viral vectors comprising a transgene encoding a biologically active human lysosomal enzyme that are able to infect and / or transfect and sustain expression of the biologically active human lysosomal enzyme transgene in mammalian cells deficient therein. In addition, methods are provided for providing a biologically active human lysosomal enzyme to cells deficient therein, which comprises introducing into the cells a vector comprising and expressing a transgene encoding the biologically active human lysosomal enzyme, wherein the vector is taken up by the cells, the transgene is expressed and biologically active enzyme is produced. The cells may be infected and / or transfected by the vector, dependent upon whether the vector is a viral vector and / or plasmid or the like. The invention also provides a method of supplying a biologically active human lysosomal enzyme to other distant cells deficient therein wherein the transfected and / or infected cells harboring the vector secrete the biologically active enzyme which is then taken up by the other deficient cells. In a preferred embodiment the present invention provides for sustained production of biologically human active α-galactosidase A in cells of Fabry individuals that are deficient in said enzyme.

Description

RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 10 / 244,700, filed Sep. 13, 2002, which is a continuation of U.S. application Ser. No. 09 / 496,499, filed Feb. 2, 2000, which is a continuation of U.S. application Ser. No. 09 / 182,245, filed Oct. 29, 1998, now U.S. Pat. No. 6,066,626, which claims the benefit of U.S. Provisional Application No. 60 / 063,527, filed Oct. 29, 1997, now abandoned. The entire teachings of the above applications are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Lysosomal storage diseases are a group of over 40 disorders which are the result of defects in genes encoding enzymes that break down glycolipid or polysaccharide waste products within the lysosomes of cells. The enzymatic products, e.g., sugars and lipids, are then recycled into new products. Each of these disorders results from an inherited autosomal or X-linked recessive trait which affects the levels of enzymes in the lysosome. Generally, t...

AI Technical Summary

Benefits of technology

[0011]In a preferred embodiment the present invention provides for sustained production of biologically human active α-galactosidase A in cells of Fabry individuals that are deficient in said enzyme.

Problems solved by technology

In such diseases the deficiency in enzyme function creates a progressive systemic deposition of lipid or carbohydrate substrate in lysosomes in cells in the body, eventually causing loss of organ function and death.

There are no effective treatments currently available for this disease.

However, to date, the biochemical and clinical effectiveness of enzyme replacement in Fabry disease, as well as other lysosomal storage diseases, has not been demonstrated due to the lack of sufficient human enzyme for adequate doses and long-term evaluation.

To date, however, there has not been a vector composition that has proven capable of transducing and sustaining expression of the human. β-galactosidase A gene, or most other genes encoding lysosomal enzymes to cells that are deficient therein.

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