Methods of treating parkinson's disease using viral vectors

Patent metadata

Field	Value
Publication number	US-2018243249-A1
Application number	US-201715728570-A
Country	US
Kind code	A1
Filing date	Oct 10, 2017
Priority date	May 27, 1998
Publication date	Aug 30, 2018
Grant date	—

Abstract

Methods of delivering viral vectors, particularly recombinant adeno-associated virus (rAAV) virions, to the central nervous system (CNS) using convection enhanced delivery (CED) are provided. The rAAV virions include a nucleic acid sequence encoding a therapeutic polypeptide. The methods can be used for treating CNS disorders such as for treating Parkinson's Disease.

First claim

What is claimed is:

1 . A method for delivering recombinant AAV virions to a subject, comprising administering via convection-enhanced delivery (CED) said rAAV virions into the CNS of the subject, wherein said rAAV virions comprise a nucleic acid sequence encoding a therapeutic polypeptide.

2 . The method of claim 1 , wherein the administering is done with an osmotic pump.

3 . The method of claim 1 , wherein the administering is done with an infusion pump.

4 . The method of claim 1 , wherein the nucleic acid sequence encodes an aromatic-amino-acid decarboxylase (AADC).

5 . The method of claim 1 wherein the subject is a human.

6 . The method of claim 1 , wherein the rAAV virions are administered into the striatum.

7 . A method for delivering recombinant AAV virions to a subject having a CNS disorder, comprising administering via convection-enhanced delivery (CED) said virions into the CNS of the subject, wherein said virions comprise a nucleic acid sequence encoding a therapeutic polypeptide.

8 . The method of claim 7 wherein the CNS disorder is Parkinson's disease, the rAAV virions are administered into the striatum and wherein the nucleic acid sequence encodes AADC

9 . A method for treating a neurodegenerative disease in a subject, said method comprising:
(a) providing a preparation comprising recombinant adeno-associated virus (rAAV) virions, wherein said virions comprise a nucleic acid sequence that is expressible in transduced cells to provide a therapeutic effect in the subject; and (b) delivering the preparation to the CNS of the subject using convection-enhanced delivery (CED), wherein said virions transduce neural cells and the nucleic acid sequence is expressed to provide a therapeutic effect in the subject suitable for treating said neurodegenerative disease.

10 . The method of claim 9 , wherein the neurodegenerative disease is Parkinson's disease.

11 . The method of claim 9 , wherein the nucleic acid sequence expressible in transduced cells encodes AADC or functional fragment thereof.

12 . The method of claim 9 , further comprising administering to the subject at least one additional therapeutic compound.

13 . The method of claim 12 wherein the at least one additional therapeutic compound is L-dopa.

14 . The method of claim 13 , further comprising administering L-dopa and, optionally, carbidopa to the subject.

15 . A method of determining levels of dopamine activity in the brain of subject comprising;
(a) administering a labeled tracer to the subject, wherein binding of the tracer to a cell is indicative of dopamine activity; and (b) imaging the subject's brain to determine the number of cells which bind the labeled tracer, thereby determining levels of dopamine activity in the subject's brain.

16 . The method of claim 15 , wherein the labeled tracer is 6-[ 18 F]-fluoro-L-m-tryosine ( 18 F-FMT).

17 . The method of claim 15 , wherein the imaging is positron emission tomograph (PET) imaging.

Assignees

• Genzyme Corp
• Univ California

Inventors

• Bankiewicz Krystof
• Cunningham Janet

Classifications

• A61K51/00

  Preparations containing radioactive substances for use in therapy or testing in vivo · CPC title

• A61K48/0075

  characterised by an aspect of the delivery route, e.g. oral, subcutaneous · CPC title

• C12N15/86

  Viral vectors · CPC title

• C12Y401/01028

  Aromatic-L-amino-acid decarboxylase (4.1.1.28), i.e. tryptophane-decarboxylase · CPC title

• A61K38/51

  Lyases (4) · CPC title