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Compositions and methods for treating neurological disorders

A technology for disorders and neurological diseases, applied in botany equipment and methods, biochemical equipment and methods, chemical instruments and methods, etc., can solve problems such as unfulfilled hopes

Inactive Publication Date: 2018-07-31
CODA BIOTHERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] However, few delivery systems have been shown to be safe and effective; thus, the promise of gene therapy for the treatment of neurological disorders, including pain management, has not yet been realized

Method used

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  • Compositions and methods for treating neurological disorders
  • Compositions and methods for treating neurological disorders
  • Compositions and methods for treating neurological disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0432] Example 1. Construction of hSYN1-GlyR αalpha1 F207A / A288G AAV vector.

[0433] Cloning of V272-pFB-inCap6(Y705+Y731F+T492V)-inRep-Kan

[0434] A 390 bp cap6 fragment containing the introduced SbfI site and mutation (T492V) was PCR amplified using primers 2793F and 2794R. A 440 bp cap6 fragment containing the introduced BsiWI site and mutation (T492V) was PCR amplified using primers 2795F and 2796R. Amplified products were separated and purified by gel electrophoresis.

[0435] The purified 390bp and 440bp PCR products were subjected to overlap PCR to generate an 810bp cap6 fragment with primers 2793F and 2796R. Amplified products were separated and purified by gel electrophoresis.

[0436] The purified 810 bp cap6 fragment was digested with SbfI and BsiWI and ligated into the V220 vector digested with SbfI and BsiWI to generate V272-pFB-inCap6(Y705+731F+T492V)-inRep-Kan.

[0437] Primer sequence:

[0438] Primer

Primer sequence 5' to 3'

SEQ ID NO: ...

example 2

[0446] Example 2. Treatment of rodent models of chronic pain.

[0447] Induction and treatment of chronic pain

[0448]Day 0: Induce chronic pain in the rodent trigeminal ganglion or dorsal root ganglion using established peripheral nerve injury methods such as chronic constriction injury (CCI, CCI / CFA) or sparing nerve injury (SNI) models. See Bennett & Xie. Pain. 1988, Decosterd & Woolf. Pain. 2000, and Imamura, Kawamoto, & Nakanishi. Brain Research Experiments (Exp. BrainRes.) 1997. In some cases, nerve damage may occur following viral vector injection.

[0449] Day 7: Inject 10 intraganglionally or intrathecally in a volume of approximately 1.0-10 μL in one or more dorsal root ganglia or trigeminal ganglion using published methods. 8 -10 10 An AAV6(Y705F+Y731F+T492V)-HSYN-GLYR(F207A / A288G)-FLAG or AAV6-GLY(HSYN-GLYR(F207A / A288G)-FLAG vector genome. See Witte, O'Hara, Sandberg ( Vit, Ohara, Sundberg et al. Mol Pain. 2009 and Towne, Fischer, Kostic et al. J Neurosci Met...

example 3

[0455] Example 3. Treating a patient with chronic pain.

[0456] Patients suffering from chronic pain are treated using the compositions and methods disclosed herein. The patient was treated with a volume of 12.0 mL of 10 15 AAV-hSYN1-hM4Di vector genomes were processed into the subarachnoid space (ie, intrathecally) of the spinal cord. In this example, the AAV vector encodes the human muscarinic DREADD hM4Di under the control of the human synapsin-1 (SYN1) promoter for selective neuronal expression. Two weeks after the injection, the patients returned to the clinic for a clozapine-N-oxide (CNO) prescription. Patients self-administered 100 μM CNO orally as needed (ie, during pain episodes).

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Abstract

The present invention generally provides vectors, compositions, and methods of using the same for treating neurological disorders, including managing pain. The compositions and methods include the useof G protein-coupled receptors and ligand-gated ion channels to treat neurological indications including pain, epilepsy and satiety disorders. The compositions and methods further include the use ofsynthetic ligands to activate the G protein-coupled receptors and ligand-gated ion channels in the treatment of neurological disease.

Description

[0001] This application claims priority and benefit to U.S. Provisional Patent Application No. 62 / 220,077, filed September 17, 2015, and U.S. Provisional Patent Application No. 62 / 220,087, filed September 17, 2015. The entire contents of both applications are incorporated herein by reference. [0002] Description of text files submitted electronically [0003] The entire contents of the text file submitted electronically are incorporated herein by reference: Copy of the Sequence Listing in computer readable format (file name: SWCH_004_01WO_SeqList_ST25.txt, date of record: September 16, 2016, file size 14.6 kilobytes). technical field [0004] The present invention generally relates to viral vectors, compositions, and related methods of use encoding receptors for the treatment of neurological disorders, including the management of pain. Background technique [0005] Neurological disorders affect hundreds of millions of people worldwide. There are currently more than 600 d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5513C12N15/861A61P3/04A61P25/14A61P25/28A61K38/08A61K38/095
CPCA61K31/5513C07K14/72C12N2750/14143C12N2750/14171C12N2830/002C12N2830/008A61K31/485A61K38/08A61K38/10A61K38/1709A61K38/177A61P25/28A61P25/16A61K31/366A61K38/095A61K2300/00A61K31/37A61K31/7048A61K45/06A61P25/00A61P25/04C12N15/861A61K9/0019C07K14/705
Inventor K·P·格林伯格N·戴维M·H·芬纳
Owner CODA BIOTHERAPEUTICS INC
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