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Last Updated: March 28, 2024

Patent: 6,187,756


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Summary for Patent: 6,187,756
Title: Composition and methods for treatment of neurological disorders and neurodegenerative diseases
Abstract:It has been discovered that the stimulation of .beta.-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising .beta.-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by .beta.-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E.sub.2 (PG E.sub.2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of .beta.-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E.sub.2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer\'s Disease.
Inventor(s): Lee; Robert K. K. (Boston, MA), Wurtman; Richard J. (Boston, MA)
Assignee: The Massachusetts Institute of Technology (Cambridge, MA)
Application Number:09/493,228
Patent Claims:see list of patent claims

Details for Patent 6,187,756

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Amgen, Inc. NEUPOGEN filgrastim Injection 103353 02/20/1991 ⤷  Try a Trial 2016-09-05
Amgen, Inc. NEUPOGEN filgrastim Injection 103353 06/28/2000 ⤷  Try a Trial 2016-09-05
Partner Therapeutics, Inc. LEUKINE sargramostim For Injection 103362 03/05/1991 ⤷  Try a Trial 2016-09-05
Partner Therapeutics, Inc. LEUKINE sargramostim Injection 103362 03/05/1991 ⤷  Try a Trial 2016-09-05
Pharmacia & Upjohn Company Llc ATGAM lymphocyte immune globulin, anti-thymocyte globulin (equine) Injection 103676 12/04/1996 ⤷  Try a Trial 2016-09-05
Jubilant Hollisterstier Llc N/A positive skin test control-histamine Injection 103891 03/13/1924 ⤷  Try a Trial 2016-09-05
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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