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Therapeutic approaches for treating cmt and related disorders

a technology of cmt and related disorders, applied in the field of treatment of charcotmarietooth disease and related disorders, can solve problems such as invalidation of diseases, and achieve the effect of reducing pmp22 expression

Inactive Publication Date: 2015-06-11
PHARNEXT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0020]Another object of the invention relates to the use of a combination of at least two compounds selected from Acetazolamide; Aminoglutethimide; Aztreonam; Baclofen Balsalazide; Bicalutamide; Bromocriptine; Bumetanide; Buspirone; Ciprofloxacin; Clonidine; Cyclosporine A; Disulfiram; Exemestane; Felbamate; Fenofibrate; Finasteride; Flumazenil; Flunitrazepam; Furosemide; Gabapentin; Galantamine; Haloperidol; Ibuprofen; Isoproterenol; L-carnitine; Liothyronine (T3); Losartan; Loxapine; Metaproterenol; Metaraminol; Metformin; Methimazole; Methylergonovine; Metopirone; Metoprolol; Mifepristone; Montelukast; Nadolol; Naltrexone; Naloxone; Norfloxacin; Pentazocine; Phenoxybenzamine; Phenylbutyrate; Pilocarpine; Pioglitazone; Prazosin; Raloxifene; Rifampin; Simvastatin; Spironolactone; Tamoxifen; Trilostane; Valproic acid; Carbamazepine; Ketoprofen; Flurbiprofen; Diclofenac; Meloxicam; D-Sorbitol; Tacrolimus; Diazepam; Dutasteride; Indomethacin; Dinoprostone; Carbachol; Estradiol; Curcumin; Lithium; Rapamycin; Betaine; Trehalose; Amiloride; Albuterol, or salts or prodrugs thereof, for (the manufacture of a medicament for) reducing PMP22 expression in a subject having CMT or a related disorder.

Problems solved by technology

The disease is invalidating with cases of accompanying neurological pain and extreme muscular disability.

Method used

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  • Therapeutic approaches for treating cmt and related disorders
  • Therapeutic approaches for treating cmt and related disorders
  • Therapeutic approaches for treating cmt and related disorders

Examples

Experimental program
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examples

1. Cell Culture

[0196]1.1: Commercially Available Rat Primary Schwann Cells

[0197]Vials of rat Schwann cells (SC) primary culture (Sciencell #R1700) are defrost and seeded at the density of 10,000 cells / cm2 in “Sciencell Schwann cell medium” (basal medium from Sciencell #R1701) in poly-L-lysine pre-coated 75 cm2 flasks. The culture medium is composed of basal medium, 5% Fetal Bovine Serum (3H-Biomedical AB #1701-0025), 1% Schwann cell growth supplement (3H Biomedical AB #1701-1752), 1% Gentamicin (Sigma #G1397) and 10 μM of Forskolin (Sigma #F6886) to promote their proliferation.

[0198]After reaching confluency (4 to 10 days depending on cell batch), Schwann cells are purified by gentle agitation or by thy1.1 immunopanning that allow SC isolation from adherent fibroblasts, to produce cultures that are at least 95% pure. SC are then counted (Tryptan blue method) and seeded in poly-L-lysine pre-coated 75 cm2 flask in the same SC medium. At confluency, cells are rinsed, trypsinized (tryps...

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Abstract

Compositions and methods for the treatment of Charcot-Marie-Tooth disease and related disorders. Also provided are combination therapies for treating this disease by decreasing PMP22 expression in a subject.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of U.S. application Ser. No. 12 / 744,962, filed on May 27, 2010, which is the National Stage of International Application No. PCT / EP2008 / 066468, filed on Nov. 28, 2008, which claims the priority of U.S. Provisional Application No. 60 / 991,800, filed on Dec. 3, 2007, and European Application No. 07301614.9, filed on Nov. 30, 2007. The content of the aforementioned applications is incorporated herein by reference in its entirety.BACKGROUND[0002]1. Field of the Invention[0003]The present invention relates to compositions and methods for the treatment of the Charcot-Marie-Tooth disease and related disorders.[0004]2. Background Information[0005]Charcot-Marie-Tooth disease (“CMT”) is an orphan genetic peripheral poly neuropathy. Affecting approximately 1 in 2,500 individuals, this disease is the most common inherited disorder of the peripheral nervous system. Its onset typically occurs during the first or second...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/485A61K31/197A61K31/047
CPCA61K31/485A61K31/197A61K31/047A61P25/00A61K9/20A61K9/48A61P25/02A61K9/08A61K9/4866A61K31/7004A61K31/395A61K9/0095A61K2300/00A61K47/06A61K9/0053
Inventor COHEN, DANIELCHUMAKOV, ILYAGUERASSIMENKO, OXANANABIROCHKIN, SERGUEI
Owner PHARNEXT
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