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Therapeutic Use of LARGE in Treating Muscular Dystrophy

Detailed Technology Description
Inventor: Kevin CampbellInvestigator, Howard Hughes Medical InstituteRoy J. Carver Professor of Physiology & Biophysics and Neurology http://www.physiology.uiowa.edu/campbell/
*Abstract

Background

Researchers at the University of Iowa have identified a new method for preventing and treating muscular dystrophy through the therapeutic use of LARGE.  Muscular dystrophy (MD) is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion.  MD, which is largely inherited, affects an estimated 30,000 patients in the United States.  Worldwide, one in every 3,500 males is affected by the disease, with some types of MD more prevalent in certain regions than others.   There are several pharmaceutical and therapeutic treatments that can slow the progression of MD, but no cure for any form of the disease.  

     

Technology

A new method for preventing and treating muscular dystrophy through gene therapy has been developed by scientists at the University of Iowa.  The patented approach involves restoring the normal functionality of alpha-dystroglycan – a protein that plays a key role in the structural integrity of muscle cells.  By introducing the LARGE gene (or other glycosyltransferases) to muscle tissue through injections of cDNA constructs or expressible RNA, researchers have not only been able to prevent muscular degeneration but also restore the synthesis of properly functioning alpha-dystroglycan in impaired tissue.

       

Advantages

Because distinct muscular dystrophies are caused by mutations in different proteins, treatments have traditionally developed to target just one or two distinct versions of the disease. The use of glycosyltransferases is exciting in that it holds the potential to restore and/or protect the function of muscle cells regardless of the source of MD mutation.  As a result, this approach can be used in the treatment of Duchenne muscular dystrophy, Becker muscular dystrophy, Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, and limb-girdle muscular dystrophy.  The technology can also be used to treat age-related or injury-related weakness or muscle atrophy.

     

          ·         Potentially curative gene therapy to treat multiple forms of muscular dystrophy

 

          ·         Preventive applications for patients genetically predisposed to muscular dystrophy

     

          ·         Technology also effective in treating age/injury-related muscle degeneration

 

Relevant Research

Barresi R, et al.  LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies.  Nat Med.  2004 Jul;10(7):696-703. http://www.ncbi.nlm.nih.gov/pubmed/15184894.

      

Kanagawa M, et al.  Molecular recognition by LARGE essential for expression of dystroglycan. Cell.  2004 Jun 25;117(7):953-64. http://www.ncbi.nlm.nih.gov/pubmed/15210115.

      

Patent Link

patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN/8119766

*Licensing
Kellen SensorSenior Licensing Associate University of Iowa Research FoundationEmail:    kellen-sensor@uiowa.eduPhone:   (319) 335-4073
Country/Region
USA

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