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METHOD AND COMPOSITION FOR GENERATING BASAL FOREBRAIN CHOLINERGIC NEURONS (BFCNs)

a technology of basal forebrain cholinergic neurons and cholinergic neurons, which is applied in the field of medicine to achieve the effect of efficient derive bfcns

Pending Publication Date: 2021-05-06
NEW YORK STEM CELL FOUND INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a reliable way to produce BFCNs (brain flourishing cells) from pluripotent stem cells, such as ESCs and iPSCs. This process is efficient and results in high reproduction.

Problems solved by technology

Unfortunately, we only have direct evidence for genetic causation that accounts for 3-5% of these patients.

Method used

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  • METHOD AND COMPOSITION FOR GENERATING BASAL FOREBRAIN CHOLINERGIC NEURONS (BFCNs)
  • METHOD AND COMPOSITION FOR GENERATING BASAL FOREBRAIN CHOLINERGIC NEURONS (BFCNs)
  • METHOD AND COMPOSITION FOR GENERATING BASAL FOREBRAIN CHOLINERGIC NEURONS (BFCNs)

Examples

Experimental program
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example i

CRISPR / Cas9-Correctable Mutation-Related Molecular and Physiological Phenotypes in iPSC-Derived Alzheimer's PSEN2N141I Mutation

[0082]Basal forebrain cholinergic neurons (BFCNs) are believed to be one of the first cell types to be affected in all forms of AD, and their dysfunction is clinically correlated with impaired short-term memory formation and retrieval. We present an optimized in vitro protocol to generate human BFCNs from iPSCs, using cell lines from presenilin 2 (PSEN2) mutation carriers and controls. As expected, cell lines harboring the PSEN2N141I mutation displayed an increase in the Aβ42 / 40 in iPSC-derived BFCNs. Neurons derived from PSEN2N141I lines generated fewer maximum number of spikes in response to a square depolarizing current injection. The height of the first action potential at rheobase current injection was also significantly decreased in PSEN2N141I BFCNs. CRISPR / Cas9 correction of the PSEN2 point mutation abolished the electrophysiological deficit, restorin...

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Abstract

The invention relates to methods and compositions for developing basal forebrain cholinergic neurons (BFCNs) from stem cells, and in particular, BFCNs having repaired electrophysiological defects relating to one or more mutations in PSEN2, and to the use of such BFCNs in cell-based therapies to treat Alzheimer's disease.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation application of U.S. application Ser. No. 15 / 990,208 filed May 25, 2018, now issued as U.S. Pat. No. 10,889,800; which claims the benefit under 35 USC § 119(e) to U.S. Application Ser. No. 62 / 586,571 filed Nov. 15, 2017, U.S. Application Ser. No. 62 / 574,639 filed Oct. 19, 2017, U.S. Application Ser. No. 62 / 571,741 filed Oct. 12, 2017 and U.S. Application Ser. No. 62 / 511,271 filed May 25, 2017, all now expired. The disclosure of each of the prior applications is considered part of and is incorporated by reference in the disclosure of this application.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under Grant Nos. AG005138, AG046170 and AG042965 awarded by the National Institutes of Health. The government has certain rights in this invention.INCORPORATION OF SEQUENCE LISTING[0003]The material in the accompanying sequence listing is hereby...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N5/0793C12N15/11C12N9/22A61K35/30G01N33/50C12N5/074
CPCC12N5/0619C12N2510/00C12N9/22A61K35/30G01N33/5058C12N5/0696C12N2506/45C12N2501/999C12N2800/80C12N2310/20G01N2800/2814C12N2506/02C12N2501/15C12N2501/41C12N15/11
Inventor NOGGLE, SCOTTORTIZ-VIRUMBRALES, MAITANEGANDY, SAMKRUGLIKOV, ILYAEHRLICH, MICHELLE
Owner NEW YORK STEM CELL FOUND INC
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