Methods and compositions for improving cognitive function

Inactive Publication Date: 2010-04-22
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007]In accordance with a third aspect of the present invention, there is provided a pharmaceutical composition for improving cognitive function in a subject with age-related cognitive impairment or at risk thereof, the composition comprising a SV2A inhibitor or a pharmaceutically acceptable salt thereof. In certain embodiments of the invention, the SV2A inhibitor is present in an amount of 5-140 mg. In other embodiments of the invention, the SV2A inhibitor is present in an amount of 0.7-180 mg.
[0008]In accordance with a fourth aspect of the present invention, there is provided a pharmaceutical composition for improving cognitive function in a subject with age-related cognitive impairment or at risk thereof, the composition comprising a SV2A inhibitor or a pharmaceutically acceptable salt thereof and valproate or an analog or a derivative or a pharmaceutically acceptable salt thereof. In certain embodiments of the invention, the SV2A inhibitor is present in an amount of 3-50 mg. In other embodiments of the invention, the SV2A inhibitor is present in an amount of 0.07-50 mg.
[0009]In accordance with a fifth aspect of the present invention, there is provided a method for treating age-related cognitive impairment in a subject in need or at risk thereof, the method comprising the step of administering to said subject a therapeutically effective amount of levetiracetam or a pharmaceutically acceptable salt thereof. In certain embodiments of the invention, levetiracetam or a pharmaceutically acceptable salt thereof is administered every 12 or 24 hours at a daily dose of about 1-2 mg/kg. In certain embodiments of the invention, levetiracetam or a pharmaceutically acceptable salt thereof is administered every 12 or 24 hours at a daily dose of about 70-150 mg. In some embodiments of the invention, levetiracetam or a pharmaceutically acceptable salt thereof is administered every 12 or 24 hours at a daily dose of about 0.1-2.5 mg/kg. In some embodiments of the invention, levetiracetam or a pharmaceutically acceptable salt thereof is administered every 12 or 24 hours at a daily dose of about 7-180 mg. In some embodiments of the invention, levetiracetam or a pharmaceutically acceptable salt thereof is administered every 12 or 24 hours at a daily dose of about 0.4-2.5 mg/kg. In some embodiments of the invention, levetiracetam or a pharmaceutically acceptable salt thereof is administered every 12 or 24 hours at a d

Problems solved by technology

Moreover, a significant population of elderly adults experiences a dec

Method used

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  • Methods and compositions for improving cognitive function
  • Methods and compositions for improving cognitive function
  • Methods and compositions for improving cognitive function

Examples

Experimental program
Comparison scheme
Effect test

example 1

Increased Gene Expression of SV2A in Aged-Impaired Rats

Behavioral Characterization of Young, Aged-Impaired and Aged-Unimpaired Rats in Morris Water Maze (MWM)

[0899]Behavioral tests were performed on young (4 months old) and aged (24 months old) pathogen-free male Long-Evans rats.

[0900]The MWM apparatus consists of a large, circular pool (diameter 1.83 m; height, 0.58 m) filled with water (27° C.) that is made opaque through the addition of non-toxic pigment or some other substance. In the typical “hidden platform” version of the test, rats are trained to find a camouflaged white escape platform (height, 34.5 cm) that is positioned in the center of one quadrant of the maze about 1.0 cm below the water surface. This platform can be retracted to the bottom of the tank or raised to its normal position from outside the maze during behavioral testing. The location of the platform remains constant from trial to trial. Because there are no local cues that mark the position of the platform, ...

example 2

Effect of Levetiracetam in Aged-Impaired Rats

Morris Water Maze Results

[0917]Six Age-Impaired (AI) Long-Evans rats (as characterized above) were tested for their memory of new spatial information in the MWM, under different drug / control treatment conditions (vehicle control and two different dosage levels of levetiracetam). The MWM protocol was substantially the same as the one described in Example 1. Specifically for this study, a retention trial was performed after the training trials, as described below.

[0918]AI rats were given six training trials per training day with a 60-sec inter-trial interval between each training trial for two consecutive days. On each training trial, the rat was released in the maze from one of four equally spaced starting positions around the perimeter of the pool. If the rat did not locate the escape platform within 90 sec on any trial, the experimenter guided the rat to the platform, where it remained for 30 sec. 30 minutes to 1 hour prior to all the tr...

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Abstract

This invention relates to treating age-related cognitive impairment. This invention in particular relates to the use of inhibitors of synaptic vesicle protein 2A (SV2A), such as levetiracetam, seletracetam, and brivaracetam, in improving cognitive function in subjects that exhibit age-related cognitive impairment or are at risk thereof, including, without limitation, subjects having or at risk for Mild Cognitive Impairment (MCI), Age-related Cognitive Decline (ARCD) or Age-Associated Memory Impairment (AAMI).

Description

[0001]This application claims priority and benefit from U.S. Provisional Patent Applications 61 / 105,847 (filed Oct. 16, 2008), 61 / 152,631 (filed Feb. 13, 2009) and 61 / 175,536 (filed May 5, 2009). The contents and disclosures of each of these prior provisional applications are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]This invention relates to methods and compositions for treating age-related cognitive impairment. In particular, it relates to the use of inhibitors of synaptic vesicle glycoprotein 2A (SV2A) in treating age-related cognitive impairment in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI) or Age Related Cognitive Decline (ARCD).BACKGROUND OF THE INVENTION[0003]Cognitive ability may decline as a normal consequence of aging. Moreover, a significant population of elderly adults experiences a decline in cognitive abi...

Claims

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Application Information

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IPC IPC(8): A61K31/40A61P25/00
CPCA61K31/19A61K31/20A61K31/4015A61K2300/00A61P25/00A61P25/28A61P35/00A61P43/00
Inventor GALLAGHER, MICHELAHABERMAN, REBECCAKOH, MING TENG
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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