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Successful Gene Replacement Therapy in Mice with Menkes Disease

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Menkes disease is a lethal brain condition that affects 1 out of 50,000 to 100,000 newborns each year. Infants with severe cases often die very early in life, and most children with Menkes disease do not survive beyond age 3. 

Menkes occurs in infants that are born with a mutated form of the gene ATP7A. The function of the normal gene is to help the body process copper, which is necessary for normal development throughout the body. In children with Menkes disease, ATP7A does not work properly and the trace amounts of copper needed for development are not available. The lack of copper has the greatest affect in the brain.   

Copper injections are the only current treatment option, but this is only effective when the form of the inherited gene is less severe and ATP7A still retains some function. 

One approach for attempting to treat diseases caused by defective genes is to insert a normal version of the gene into the DNA of the individual’s cells—a procedure known as gene replacement or gene therapy.

Researchers in the Unit on Human Copper Metabolism, in the Division of Intramural’s Molecular Medicine Program, took advantage of a mouse model of Menkes disease to test the gene replacement strategy. This mouse model carries a mutant Atp7a gene, and the mouse pups die by age 14 days due to abnormal copper transport.  The researchers injected a normal Atp7a gene into the brains of the Menkes mice using a harmless virus that carries the normal gene into brain cells. Mice receiving the normal gene had improved copper processing and lived several days longer than untreated mice. 

The researchers then treated a group of mice with the gene replacement therapy followed by the injection of a dose of copper. Mice receiving this combined treatment showed a significant response to treatment, on average, surviving three times longer than the untreated mice with 20% of the mice living for a remarkable ten months.

The study is an encouraging step towards developing a powerful new treatment that may offer hope for children with Menkes disease as well as other genetic diseases with major effects in the brain (PMID: 21878905).

Last Reviewed: 05/01/2014

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Vision National Institutes of Health Home BOND National Institues of Health Home Home Storz Lab: Section on Environmental Gene Regulation Home Machner Lab: Unit on Microbial Pathogenesis Home Division of Intramural Population Health Research Home Bonifacino Lab: Section on Intracellular Protein Trafficking Home Lilly Lab: Section on Gamete Development Home Lippincott-Schwartz Lab: Section on Organelle Biology