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Use of activity dependent neurotrophic factor for enhancing learning and memory: pre-and post-natal administration

a neurotrophic factor and activity-dependent technology, applied in the field of pre- and post-natal administration, can solve the problems of uncertain efficacy of these compounds in normal people, and achieve the effect of improving short term memory and reference memory

Inactive Publication Date: 2009-08-13
THE GOVERNMENT OF THE US SEC THE DEPT +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for improving performance, such as learning and memory, in subjects by administering a specific type of protein called Activity Dependent Neurotrophic Factor (ADNF) polypeptides. These polypeptides have been shown to have potent neuroprotective and growth-promoting functions in animal models. When administered to subjects either prenatally or postnatally, the polypeptides can enhance their learning and memory abilities. The invention can be applied to improve the performance of subjects with neuropathology, sensory-motor problems, and memory deficiencies. The polypeptides can also be used as a treatment for individuals with fragile X syndrome or other genetic defects. The patent provides various methods for measuring the improvement in performance caused by the polypeptides. Overall, the invention provides a way to improve the learning and memory of subjects and to promote brain health.

Problems solved by technology

In addition, efficacy of these compounds in normal people is uncertain.

Method used

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  • Use of activity dependent neurotrophic factor for enhancing learning and memory: pre-and post-natal administration
  • Use of activity dependent neurotrophic factor for enhancing learning and memory: pre-and post-natal administration
  • Use of activity dependent neurotrophic factor for enhancing learning and memory: pre-and post-natal administration

Examples

Experimental program
Comparison scheme
Effect test

example i

Enhanced Learning and / or Memory after Postnatal Administration of an ADNF Polypeptide

[0144]Example I describes properties of the ADNF polypeptides, such as SALLRSIPA (“ADNF-9”; SEQ ID NO:1), derived from ADNF I, and NAPVSIPQ (“NAP”; SEQ ID NO:2), derived from ADNF-III or ADNP, in control animals or animals exposed to the cholinotoxin, ethylcholine aziridium (AF64A), a blocker of choline uptake (Fisher et al., Neurosci. Lett. 102:325-331 (1989)). An intact cholinergic system is required for normal brain function, whereas Alzheimer's disease is associated with the death of cholinergic cells (Brumback and Leech, 1994). Thus, rats treated with AF64A provide an accepted model for testing in vivo efficacy of drugs that protect against cognitive impairments, that may result from cholinotoxicity (Fisher et al., Neurosci. Lett. 102:325-331 (1989); Gozes et al., Proc. Natl. Acad Sci. U.S.A. 93:427-432 (1996); Gozes et al., Proc. Natl. Acad. Sci. U.S.A. 96:4143-4148 (1999)). The experiments de...

example ii

Prenatal Administration of ADNF Polypeptides Provides Postnatal Enhanced Learning and / or Memory

[0184]Materials and Methods

[0185]Animals and Treatment

[0186]C57-B16J female mice (Jackson Labs) were kept under a 12 h light, 12 h dark regimen with food and water available at all times. The mice received humane animal care in compliance with the “Guideline for Care and Use of Experimental Animals.” Six week old females (21-24 grams) were mated with C57-B16J males for 4 h. The presence of a vaginal plug was considered day 0 pregnancy.

[0187]Animals were injected intraperitoneally on pregnancy day 8, or treated on pregnancy day 8 after 1 hour fast with gavage dose of ADNF polypeptides. NAP was diluted in 50 μl DMSO and diluted in filtered Dulbecco's phosphate buffered saline (DPBS). SAL was dissolved and diluted in filtered DPBS. Control animals were treated with a vehicle (i.e., DPBS). All treatments were coded.

[0188]Delivery occurred on day 20, weaning on day 20 of life. Male offspring we...

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Abstract

The present invention provides methods for improving performance (e.g., learning and / or memory) using ADNF polypeptides, by treating the subject prenatally or postnatally with an Activity Dependent Neurotrophic Factor (ADNF) polypeptide in an amount sufficient to improve postnatal learning and / or memory of the subject.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. National Phase application Ser. No. 10 / 296,849, filed Aug. 27, 2002, which is a National Phase Application under 35 U.S.C. § 371 of Application No. PCT / US2001 / 17758, filed May 31, 2001, which claims priority to U.S. Provisional Application No. 60 / 208,944 filed May 31, 2000. All of these applications are incorporated herein by reference[0002]This application is related to U.S. Ser. No. 07 / 871,973 filed Apr. 22, 1992, now U.S. Pat. No. 5,767,240; U.S. Ser. No. 08 / 342,297, filed Oct. 17, 1994 (published as WO96 / 11948), now U.S. Pat. No. 6,174,862; U.S. Ser. No. 60 / 037,404, filed Feb. 7, 1997 (published as WO98 / 35042); U.S. Ser. No. 09 / 187,330, filed Nov. 11, 1998 (published as WO00 / 27875); U.S. Ser. No. 09 / 267,511, filed Mar. 12, 1999 (published as WO00 / 53217); U.S. Ser. No. 60 / 149,956, filed Aug. 18, 1999 (published as WO01 / 12654); U.S. Ser. No. 60 / 208,944, filed May 31, 2000; and U.S. Ser. No. 60 / ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/10A61K38/08A61P25/00A61K38/00A61K38/18A61P3/10A61P9/00A61P9/10A61P17/02A61P21/04A61P25/08A61P25/14A61P25/16A61P25/18A61P25/28A61P25/32A61P31/18A61P35/00A61P43/00C07K7/06C07K7/08C07K14/475C07K14/48
CPCC07K14/475A61K38/00A61P17/02A61P21/04A61P25/00A61P25/08A61P25/14A61P25/16A61P25/18A61P25/28A61P25/32A61P31/18A61P35/00A61P43/00A61P9/00A61P9/10A61P3/10
Inventor SPONG, CATHERINE Y.BRENNEMAN, DOUGLASGOZES, IIIANA
Owner THE GOVERNMENT OF THE US SEC THE DEPT
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