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Prevention and treatment of synucleinopathic disease

a technology of synucleinopathy and disease, applied in the direction of antibody medical ingredients, carrier-bound antigen/hapten ingredients, immunological disorders, etc., can solve the problems of patient risk factor for disease and asymptomatic, and achieve the effect of improving patient motor characteristics and preventing deterioration of patient motor characteristics

Inactive Publication Date: 2011-06-09
JANSSEN ALZHEIMER IMMUNOTHERAPY +1
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Benefits of technology

[0013]In one aspect, the invention provides methods of preventing or treating a disease characterized by Lewy bodies or alpha-SN aggregation in the brain. Such methods entail, inducing an immunogenic response against alpha-SN. Such induction may be achieved by active administration of an immunogen or passive by administration of an antibody or a derivative of an antibody to synuclein. In some methods, the patient is asymptomatic. In some methods, the patient has the disease and is asymptomatic. In some methods the patient has a risk factor for the disease and is asymptomatic. In some methods, the disease is Parkinson's disease. In some methods, the disease is Parkinson's disease, and the administering the agent improves motor characteristics of the patient. In some methods, the disease is Parkinson's disease administering the agent prevents deterioration of motor characteristics of the patient. In some methods, the patient is free of Alzheimer's disease.

Problems solved by technology

In some methods the patient has a risk factor for the disease and is asymptomatic.

Method used

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  • Prevention and treatment of synucleinopathic disease
  • Prevention and treatment of synucleinopathic disease
  • Prevention and treatment of synucleinopathic disease

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I. Immunization of Human Alpha-Synuclein Transgenic Mice with Human Alpha-Synuclein Results in the Production of High Titer Anti-Alpha-Synuclein Antibodies that Cross the Blood-Brain Barrier

[0190]Full-length recombinant human alpha-SN was resuspended at a concentration of 1 mg / ml in 1× phosphate buffered saline (PBS). For each injection, 50 μl of alpha-SN was used; giving a final concentration of 50 μg per injection to which 150 μl of 1×PBS was added. Complete Freund's adjuvant (CFA) was then added 1:1 to either alpha-SN or PBS alone (control), vortexed and sonicated to completely resuspend the emulsion. For the initial injections, eight D line human alpha-SN transgenic (tg) single transgenic 4-7 months old mice (Masliah, et al. Science 287:1265-1269 (2000) received injections of human alpha-SN in CFA and, as control, four D line human alpha-SN tg mice received injections of PBS in CFA. Mice received a total of 6 injections. Three injections were performed at two weeks intervals and...

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Abstract

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. §119(e) of U.S. Application No. 60 / 423,012, filed Nov. 1, 2002, which is incorporated by reference herein for all purposes.BACKGROUND OF THE INVENTION[0002]Alpha-synuclein (alphaSN) brain pathology is a conspicuous feature of several neurodegenerative diseases, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer's disease (LBVAD), multiple systems atrophy (MSA), and neurodegeneration with brain iron accumulation type-1 (NBIA-1). Common to all of these diseases, termed synucleinopathies, are proteinaceous insoluble inclusions in the neurons and the glia which are composed primarily of alphaSN.[0003]Lewy bodies and Lewy neurites are intraneuronal inclusions which are composed primarily of alphaSN. Lewy bodies and Lewy neurites are the neuropathological hallmarks Parkinson's disease (PD). PD and other synucleinopathic diseases have been co...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K39/00A61K39/385A61P37/04A61P25/00A61BA61B1/00A61K38/17A61K45/06A61K47/48A61K51/10A61P25/16A61P25/28C12Q1/00C12Q1/02G01N33/53
CPCA61K38/1709A61K39/0007A61K2039/55566A61K51/1078A61K45/06A61P25/00A61P25/16A61P25/28A61P37/04A61P43/00
Inventor SCHENK, DALE B.MASLIAH, ELIEZER
Owner JANSSEN ALZHEIMER IMMUNOTHERAPY
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