Intraventricular enzyme delivery for lysosomal storage diseases

Patent metadata

Field	Value
Publication number	US-8926967-B2
Application number	US-17561008-A
Country	US
Kind code	B2
Filing date	Jul 18, 2008
Priority date	Jan 20, 2006
Publication date	Jan 6, 2015
Grant date	Jan 6, 2015

Abstract

Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

First claim

We claim:

1. A method of treating a patient with Niemann-Pick A or B disease, comprising: administering a single dose of an acid sphingomyelinase to the patient via intraventricular delivery to the brain in an amount sufficient to reduce sphingomyelin levels throughout said brain, wherein the step of administering the single dose is performed at a rate such that the administration of the single dose consumes more than four hours.

2. The method of claim 1 wherein the amount administered is further sufficient to reduce sphingomyelin levels in the liver of the patient.

3. The method of claim 1 wherein the amount administered is further sufficient to reduce sphingomyelin levels in the lungs of the patient.

4. The method of claim 1 wherein the amount administered is further sufficient to reduce sphingomyelin levels in the spleen of the patient.

5. The method of claim 1 wherein the amount administered is sufficient to reduce at least 10% of sphingomyelin levels in the brain of the patient.

6. The method of claim 5 where in the amount administered is sufficient to reduce at least 20% of sphingomyelin levels in the brain of the patient.

7. The method of claim 6 wherein the amount administered is sufficient to reduce at least 30% of sphingomyelin levels in the brain of the patient.

8. The method of claim 7 wherein the amount administered is sufficient to reduce at least 40% of sphingomyelin levels in the brain of the patient.

9. The method of claim 8 wherein the amount administered is sufficient to reduce at least 50% of sphingomyelin levels in the brain of the patient.

10. The method of claim 9 wherein the amount administered is sufficient to reduce at least 60% of sphingomyelin levels in the brain of the patient.

11. The method of claim 1 wherein the step of administering employs a pump.

12. The method of claim 1 wherein the acid sphingomyelinase is administered via an indwelling catheter.

13. The method of claim 1 wherein the levels of sphingomyelin are monitored in the patient and additional acid sphingomyelinase is administered in response to the levels of sphingomyelin determined.

14. The method of claim 1 wherein the step of administering the single dose is performed at a rate such that the administration of the single dose consumes more than five hours.

15. The method of claim 14 wherein the step of administering the single dose is performed at a rate such that the administration of the single dose consumes more than six hours.

16. The method of claim 15 wherein the step of administering the single dose is performed at a rate such that the administration of the single dose consumes more than seven hours.

17. The method of claim 16 wherein the step of administering the single dose is performed at a rate such that the administration of the single dose consumes more than eight hours.

18. A method of treating a patient with a lysosomal storage disease which is caused by a lysosomal hydrolase enzyme deficiency and the deficiency leads to accumulation of the enzyme's substrate in the brain, the method comprising: administering a single dose of the enzyme to the patient via intraventricular delivery to the brain in an amount sufficient to reduce the substrate accumulated in the brain, wherein the enzyme is administered at a rate such that the administration of the single dose consumes more than four hours.

19. The method of claim 18 wherein the lysosomal storage disease is Niemann-Pick A and the enzyme is sphingomyelinase.

20. The method of claim 18 wherein the lysosomal storage disease is Niemann-Pick B and the enzyme is sphingomyelinase.

21. The method of claim 18 wherein the lysosomal storage disease is Mucopolysaccharidosis I syndrome and the enzyme is alpha-L-iduronidase.

22. The method of claim 18 wherein the lysosomal storage disease is Mucopolysaccharidosis II syndrome and the enzyme is iduronate-2-sulfatase.

23. The method of claim 18 wherein the lysosomal storage disease is Gaucher disease and the enzyme is glucocerebrosidase.

24. The method of claim 18 wherein the lysosomal storage disease is Pompe disease and the enzyme is alpha-glucosidase.

25. The method of claim 18 wherein the lysosomal storage disease is classic late infantile Batten disease (CLN2) and the enzyme is tripeptidyl peptidase.

26. The method of claim 18 wherein the rate is such that the administration of the single dose consumes more than five hours.

27. The method of claim 26 wherein the rate is such that the administration of the single dose consumes more than six hours.

28. The method of claim 27 wherein the rate is such that the administration of the single dose consumes more than seven hours.

29. The method of claim 28 wherein the rate is such that the administration of the single dose consumes more than eight hours.

Assignees

• Dodge James
• Passini Marco A
• Shihabuddin Lamya
• Cheng Seng H
• Genzyme Corp

Inventors

• Dodge James
• Passini Marco A
• Shihabuddin Lamya
• Cheng Seng H

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title