Devices, systems and methods for improving and/or cognitive function through brain delivery of siRNA
First Claim
1. A method for improving memory or cognitive function in a subject diagnosed as having a disorder in which a diminished declarative memory is a symptom, comprising intracranially administering to the subject a therapeutically effective dose of a composition that decreases the expression of a beta amyloid cleaving enzyme type 1, or BACE1, in a cell of the nervous system of the subject, wherein the composition comprises a cassette encoding a short hairpin RNA and comprising SEQ ID NOS:
- 37-40 or the short hairpin RNA encoded by said cassette, wherein the short hairpin RNA molecule specifically suppresses BACE1 gene expression in a cell of the nervous system of the subject, and wherein at least one attribute of said memory or cognitive function is improved.
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Abstract
The present invention relates to devices, systems, and methods for improving memory and/or cognitive function by brain delivery of compositions of small interfering RNA or vectors containing the DNA encoding for small interfering RNA. Such compositions can be administered using devices, systems and methods for direct delivery of the compositions to the brain, or using devices, systems, methods of delivery, and compositions that deliver small interfering RNA or vectors containing the DNA encoding the small interfering RNA across the blood-brain barrier. The present invention also provides valuable small interfering RNA vectors, and methods for reduction of BACE1 levels in the hippocampus, cerebral cortex, or other regions of the brain that have beneficial effects on improving memory and/or cognitive function in a subject.
147 Citations
13 Claims
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1. A method for improving memory or cognitive function in a subject diagnosed as having a disorder in which a diminished declarative memory is a symptom, comprising intracranially administering to the subject a therapeutically effective dose of a composition that decreases the expression of a beta amyloid cleaving enzyme type 1, or BACE1, in a cell of the nervous system of the subject, wherein the composition comprises a cassette encoding a short hairpin RNA and comprising SEQ ID NOS:
- 37-40 or the short hairpin RNA encoded by said cassette, wherein the short hairpin RNA molecule specifically suppresses BACE1 gene expression in a cell of the nervous system of the subject, and wherein at least one attribute of said memory or cognitive function is improved.
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2. A method for improving memory or cognitive function in a subject diagnosed as having a disorder in which a diminished declarative memory is a symptom, comprising reducing the expression or production of a beta amyloid cleaving enzyme type 1, or BACE1, protein in neurons of said subject by intracranial delivery of a cassette encoding a short hairpin RNA and comprising SEQ ID NOS:
- 37-40, or the short hairpin RNA encoded by said cassette, in a pharmaceutically acceptable carrier, wherein the short hairpin RNA reduces said expression or production of said BACE1 protein, and wherein at least one attribute of said memory or cognitive function is improved.
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3. A method of delivering a small interfering RNA to a location in the brain of a subject suffering from memory or cognitive impairment characterized by a diminished declarative memory comprising the steps of:
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a) surgically implanting in said subject an intracranial access delivery device; and b) infusing into said subject a vector comprising a cassette comprising SEQ ID NOS;
37-40 and encoding a short hairpin RNA or infusing the short hairpin RNA encoded by said cassette, at a predetermined site in the brain, wherein at least one attribute of said memory or cognitive impairment is improved. - View Dependent Claims (4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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Specification