Methods for Alzheimer's disease treatment and cognitive enhance

a technology of alzheimer's disease and cognitive enhancement, applied in the field of modulation of asecretase and to cognitive enhancement, can solve the problems of not addressing the progression of the disease, ineffective clinical use and with other types of cognition disorders, and improving symptomatic and transient cognition in diseased individuals, so as to reduce the production of myalgia, reduce the effect of myalgia and preferential inhibition

Inactive Publication Date: 2005-03-24
COGNITIVE RES ENTERPRISES INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0048] In one embodiment, the PKC inhibitor is a compound that inhibits PKC in peripheral tissues. As used herein, “peripheral tissues” means tissues other than brain. In another embodiment, the PKC inhibitor is a compound that preferentially inhibits PKC in peripheral tissues. In another embodiment, the PKC inhibitor is a compound that reduces myalgia associated with the administration of a ...

Problems solved by technology

Cognition disorders create a variety of problems for today's society.
Vasodilators and metabolic enhancers (e.g. dihydroergotoxine) are mainly effective in the cognition disorders induced by cerebral vessel ligation-ischemia; however, they are ineffective in clinical use and with other types of cognition disorders.
Of the nootropics for instance, piracetam activates the peripheral endocrine system, which is not appropriate for Alzheimer's disease due to the high concentration of steroids produced in patients while tacrine, a cholinergic agent, has a variety of side effects including vomiting, diarrhea, and hepatotoxicity.
Recently the cognitive state related to Alzheimer's Disease and different methods to improve memory have been the subject of various approaches and strategies, which, unfortunately, have only improved symptomatic and transient cognition in diseased individuals and have not addressed the progression of the disease.
Acetyl cholinesterase is a major brain enzyme and manipulating its levels can result in various changes to other neurological functions and cause side effects.
While these and other methods may improve cognition, at least transiently, they do not modify the disease progression, ...

Method used

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  • Methods for Alzheimer's disease treatment and cognitive enhance
  • Methods for Alzheimer's disease treatment and cognitive enhance
  • Methods for Alzheimer's disease treatment and cognitive enhance

Examples

Experimental program
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Effect test

example 1

Cell Culture

[0093] Cultured skin fibroblasts were obtained from the Coriell Cell Repositories and grown using the general guidelines established for their culture with slight modifications (Cristofalo & Carptentier, 1988; Hirashima et al., 1996). The culture medium in which cells were grown was Dulbecco's modified Eagle's medium (GIBCO) supplemented with 10% calf serum (Biofluids, Inc.). Fibroblasts from control cell lines (AC), cases AG07141 and AG06241, and a familial AD (FAD) case (AG06848) were utilized.

example 2

PKC Activators

[0094] The different tissue distributions, the apparently distinctive roles of different isozymes, and the differential involvement in pathology make it important to use pharmacological tools that are capable of preferentially targeting specific isozymes (Kozikowski et al., 1997; Hofmann, 1997). Resent research in the medicinal chemistry field has resulted in the development of several PKC activators, for instance different benzolactams and pyrollidinones. However, the currently studied bryostatin PKC activator not only has the benefit of providing isospecific activity, but also does not suffer from the set back of the previously used PKC activator, such as being tumor promoting. The bryostatin competes for the regulatory domain of PKC and engages in very specific hydrogen bond interactions within this site. Additional information on the organic chemistry and molecular modeling of this compound can be found throughout the literature.

example 3

Treatment

[0095] Cells grown to confluence in 6 cm Petri dishes for 5-7 days. On the day of the experiment, medium was replaced with DMEM without serum and left undisturbed for 2 h. Upon completion of the 2 hour serum deprivation, treatment was achieved by direct application to the medium of Bryo, BL and DMSO at the appropriate concentrations. DMSO was less than 1% in all cases. In most cases, medium was collected and processed after 3 hours of treatment for sAPP secretion. Other time points were also used to establish a time course of secretion.

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PUM

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Abstract

The present invention relates to compositions comprising a combination of PKC activators and PKC inhibitors and methods to modulate α-secretase activity; improve or enhance cognitive ability; and/or reduce neurodegeneration in individuals suffering from diseases that impair cognitive ability, particularly Alzheimer's Disease. The invention also relates to methods for improving or enhancing cognitive ability. The present invention also provides methods for increasing the generation of non-amyloidogenic soluble APP (sAPP) comprising the activation of protein kinase C (PKC) in the brain and inhibiting PKC in peripheral tissues. Macrocyclic lactones (i.e. bryostatin class and neristatin class) are preferred PKC activators and Vitamin E is a preferred PKC inhibitor for use in the inventive composition.

Description

[0001] This application is a continuation-in-part application of U.S. Non-Provisional application Ser. No. 10 / 167,491, filed on Jun. 13, 2002, which claims priority to U.S. Provisional Application No. 60 / 362,080, filed on Mar. 7, 2002.FIELD OF THE INVENTION [0002] The present invention relates to the modulation of a-secretase and to cognitive enhancement. The invention further relates to compounds for treatment of conditions associated with amyloid processing such as Alzheimer's Disease and compositions for the treatment of such conditions. BACKGROUND OF THE INVENTION [0003] Various disorders and diseases exist which affect cognition. Cognition can be generally described as including at least three different components: attention, learning, and memory. Each of these components and their respective levels affect the overall level of a subject's cognitive ability. For instance, while Alzheimer's Disease patients suffer from a loss of overall cognition and thus deterioration of each of...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/00A61K31/365A61K31/7048A61P3/02A61P3/08A61P23/00A61P25/00A61P25/08A61P25/14A61P25/16A61P25/28A61P35/00A61P39/02A61P43/00
CPCA61K31/00A61K31/355A61K31/365A61K31/366A61K2300/00A61P3/02A61P3/08A61P23/00A61P25/00A61P25/08A61P25/14A61P25/16A61P25/20A61P25/28A61P35/00A61P39/02A61P43/00
Inventor ALKON, DANIEL
Owner COGNITIVE RES ENTERPRISES INC
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