Treatment of pompe's disease

Abstract

The invention provides methods of treating Pompe's disease using human acid alpha glucosidase. A preferred treatment regime comprises administering greater than 10 mg / kg body weight per week to a patient.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001] The present application derives priority from U.S. Ser. No. 60 / 111291 filed Dec. 7, 1998, which is incorporated by reference in its entirety for all puposes. The present application is related to U.S. Ser. No. 08 / 700,760 filed Jul. 29, 1996, which derives priority from U.S. Ser. No. 60 / 001,796, filed Aug. 2, 1995, both of which are incorporated by reference in their entirety for all purposes.[0002] The present invention resides in the fields of recombinant genetics, and medicine, and is directed to enzyme-replacement therapy of patients with Pompe's disease.[0003] Like other secretory proteins, lysosomal proteins are synthesized in the endoplasmic reticulum and transported to the Golgi apparatus. However, unlike most other secretory proteins, the lysosomal proteins are not destined for secretion into extracellular fluids but into an intracellular organelle. Within the Golgi, lysosomal proteins undergo special processing to equip them to...

AI Technical Summary

Benefits of technology

0008] In one aspect, the invention provides methods of treating a patient with Pompe's disease. Such methods entail administering to the patient a therapeutically effective amount of human acid alpha glucosidase. The dosage is preferably at least 10 mg / kg body weight per week. In some methods, the dosage is at least 60 mg / kg body weight per week or at least 120 mg / kg body weight per week. In some methods, such dosages are administered on a single occasion per week and in other methods on three occasions per week. In some methods, the treatment is containued for ate least 24 weeks. Adminstration is preferably intravenous. The human acid alpha glucosidase is preferably obtained in the milk of a nonhuman transgenic mammal, and is preferably predominatly in a 110 kD form.

Problems solved by technology

The deficiency in the lysosomal protein usually results in harmful accumulation of a metabolite.

Infantile GSD II has its onset shortly after birth and presents with progressive muscular weakness and cardiac failure.

These experiments with enzyme replacement therapy for Pompe's disease were not successful.

Moreover, both the duration of treatment, and / or the amount of enzyme administered were insufficient (3-5).

Production of lysosomal enzymes from natural sources such as human urine and bovine testis is in theory possible, but gives low yields, and the enzyme purified is not necessarily in a form that can be taken up by tissues of a recipient patient.

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