Laminins, derivatives, and compositions including same and method for their therapeutic use

A laminin, therapeutic technology, applied in the field of laminin, derivatives and compositions containing them and their therapeutic applications, can solve the problems of inability to provide therapy, limiting protein bioavailability, large size, etc.

Active Publication Date: 2010-10-27
内华达高等教育系统董事会,代表内华达大学雷诺校区
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these approaches, while showing some promise in vitro or in transgenic animals, often fail to demonstrate effective results in humans, nor do they provide a means to enable therapeutic implementation in humans
Such therapeutic avenues are notoriously difficult to implement
[0017] However, it is also known that the direct administration of proteins, especially large proteins, is very difficult
For example, large size, high charge, short half-life, poor stability, high immunogenicity, and poor membrane permeability may limit the bioavailability of the administered protein

Method used

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  • Laminins, derivatives, and compositions including same and method for their therapeutic use
  • Laminins, derivatives, and compositions including same and method for their therapeutic use
  • Laminins, derivatives, and compositions including same and method for their therapeutic use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0158] Materials and Methods

[0159] animal

[0160] Wild-type (C57BL / 6), α7 integrin-deficient (C57BL / 6 background) and nestin-GFP mice (C57BL / 6 background) used in these studies, according to the University of Nevada (University of Nevada, Reno), Euthanasia was performed according to a protocol approved by the Institutional Animal Care and Use Committees of the University of Washington, Seattle.

[0161] Histology

[0162] The tibialis anterior muscle (TA) was embedded in Optimal Cutting Temperature (OCT) (Tissue-Tek; Sakura Finetek, Torrance, California, United States), and using a Leica CM1850 cryostat, 10 μm cryosections (separation ≥ 50 μm ), placed on Surgipath microscope slides (Surgipath Medical Industries, Richmond, IL). As previously reported in Rooney et al., "Severe muscular dystrophy in mice that lack dystrophin and alpha7 intergrin", J. Cell Sci. 119: 2185-2195 (2006 ), which is hereby incorporated by reference to the extent it does not conflict with th...

Embodiment 2

[0220] Materials and Methods

[0221] animal

[0222] In these studies, C57BL / 10ScSn (wild-type) and C57BL / 10ScSn-Dmdmdx / J (mdx) strain mice (Jackson Laboratories, BarHarbor, ME) were used in accordance with the Animal Care and Use Guidelines of the University of Nevada, Reno. Use in animal protocols approved by the Animal Care and Use Committee.

[0223] α7βgal + / - Isolation of myoblasts

[0224] α7βgal from 10 days old + / - The gastrocnemius muscle was removed from the mouse, and the tissue was minced with scissors. Cells were enzymatically dissociated with 1.25 mg / ml type II collagen (Worthington Biochemical Corporation, Lakewood, NJ) at 37°C for 1 hour. The slurry was gently ground and filtered through a nylon mesh. Cells were separated from muscle fiber fragments by differential centrifugation and plated on 100 mm tissue culture plates. Myoblasts were cultured in proliferation medium (Dulbecco's modified Eagle's supplemented with 10% fetal bovine serum (FBS)...

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PUM

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Abstract

In various embodiments, the present disclosure provides a method of treating a subject using laminin or a composition that includes laminin. In one embodiment, the method is used to enhance muscle regeneration, maintenance, or repair in a subject. In another embodiment, the method is used to promote wound healing. The method, in yet another embodiment, is used to prevent or reduce muscle damage or injury. In specific implementations of these methods, the laminin or composition that includes laminin is administered in a therapeutically effective amount. In some implementations, the laminin is a complete laminin protein. In other implementations, the laminin is a laminin fragment, a laminin derivative, or a laminin analogue.

Description

[0001] Cross-references to related applications [0002] This application claims priority to US Provisional Patent Application No. 60 / 998,320, filed October 9, 2007, which is incorporated by reference. [0003] statement about government support [0004] This invention was made with support from the following grants from the U.S. Government: National Institutes of Health (NIH), National Center for Research Resources, Grant Nos. NCRR P20 RR018751-01, P20 RR15581 -04; National Institute of Arthritis and Musculoskeletal and Skin Diseases, Grant No. NIAMS R01AR053697-01; and National Institute of Neurological Disorders and Stroke , Grant No. NINDSR21NS058429-01. The US Government has certain rights in this invention. technical field [0005] The present disclosure relates to methods of providing a therapeutic benefit to a subject by administering laminin or a composition comprising laminin to the subject. In particular embodiments, the present disclosure provides methods of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/195A61K38/39C07K14/78A61P43/00
CPCA61K38/39A61K45/06A61P17/02A61P21/00A61P21/04A61P43/00A61K38/1709
Inventor 迪安·J·布尔津加钦塔·E·鲁尼
Owner 内华达高等教育系统董事会,代表内华达大学雷诺校区
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