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

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 / ...

AI Technical Summary

Benefits of technology

[0006]In one embodiment of the present invention, it is discovered that upon post-natal administration, the ADNF polypeptides also improve performance, such as learning and memory, in animal models that are afflicted with, e.g., neuropathology, Alzheimer's disease, Down's syndrome, age, or mental retardation (e.g., fragile X syndrome), as well as normal animals. The polypeptides of the invention can also be used to improve short term and reference memory.

[0007]As such, applications for the ADNF polypeptides of the present invention include improving the performance of subjects with, e.g., neuropathology; sensory-motor problems; improving the performance of subjects impaired in cognitive tasks; improving the performance of subjects with memory deficiencies; improving the performance of normal subjects; and the like. Accordingly, embodiments of the invention in suitable formulations, can be employed for decreasing the amount of time needed to learn a cognitive, motor or perceptual task. Alternatively, invention compounds, in suitable formulations, can be employed for increasing the time for which cognitive, motor or perceptual tasks are retained. As another alternative, embodiments of the invention in suitable formulations, can be employed for decreasing the quantity and / or severity of errors made in recalling a cognitive, motor or perceptual task. Such treatment may prove especially advantageous in individuals who have suffered injury to the nervous system, or who have endured disease of the nervous system. ADNF polypeptides are administered to the affected individual, and thereafter, the individual is presented with a cognitive, motor or perceptual task. Moreover, ADNF polypeptides can be administered to normal subjects to improve their performance (e.g., learning and memory). ADNF polypeptides can be particularly useful for an aged population in which capacity for memory (e.g., short term) has generally declined.

[0008]In another embodiment, the present invention is based, in part, on the discovery that when animals in utero are treated with Activity Dependent Neurotrophic Factor (ADNF) polypeptides, the ADNF polypeptides improved the animals' postnatal learning and memory, in particular, spatial learning. Surprisingly, this long term effect of ADNF polypeptides is observed even when a single dose of ADNF polypeptides is prenatally administered in the beginning of pregnancy. Quite surprisingly, this enhanced learning and memory effect of ADNF polypeptides is seen even in animals with normal mental capacity (e.g., normal mice without any mental impairment). Hence, ADNF polypeptides can push normal animals beyond their natural capacity of learning and memory and can improve their cognitive skills.

[0009]As described above, these ADNF polypeptides have previously been shown to have remarkable potency and activity in animal models, particularly in those related to neurodegeneration. However, the effects of ADNF polypeptides were observed when they were postnatally administered to the animals. It has now been discovered for the first time that the prenatal treatment with ADNF polypeptides can enhance the animals' postnatal learning and memory, both for normal animals as well as for mentally impaired animals.

[0010]The present discovery has significant applications in human subjects in improving their learning, memory, and associated mental processes. Even normal human subjects can benefit from the prenatal treatment with ADNF polypeptides. Moreover, the present discovery has applications in subjects who are mentally compromised. For example, if a fetus is diagnosed as having mental retardation or Down's syndrome, the fetus in utero can be treated with ADNF polypeptides so that its postnatal learning and memory skills can be ameliorated. Even without a specific diagnosis of mental retardation or Down's syndrome, ADNF polypeptides can be prophylactically administered to the fetus in certain circumstances. For example, if there is a family history of mental retardation (e.g., fragile X syndrome), ADNF polypeptides can be prophylactically administered to the fetus in utero. In another example, if the mother is older (e.g., 35 years or older) and thus, has a higher risk of having a baby with Down's syndrome or other genetic defects, ADNF polypeptides can be prophylactically administered to the fetus in utero.

[0021]In yet another embodiment, the ADNF polypeptide improves a short term memory. In yet another embodiment, the ADNF polypeptide improves a reference memory. In yet another embodiment, the ADNF polypeptide is administered intranasally or orally.

Problems solved by technology

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

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