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Gene therapy may reverse deadly muscle wasting: scientists

Feb. 27, 2010
Courtesy of Ohio State University
and World Science staff

A deadly mus­cle-wasting dis­or­der that af­flicts chil­dren may be sus­cep­ti­ble to ef­fec­tive treat­ment through gene ther­a­py, sci­en­tists say.

Re­search in mice found that the ther­a­py could re­verse a pro­tein de­fi­cien­cy char­ac­ter­is­tic of the con­di­tion and thus cor­rect mus­cu­lar func­tion, re­store nerve sig­nals and im­prove sur­viv­al.

The mice were en­gi­neered to de­vel­op the dis­or­der, spi­nal mus­cu­lar at­ro­phy, some­times al­so called flop­py ba­by syn­drome be­cause of its strength-sapping ef­fects. The dis­ease re­sults when due to a mis­sing gene, mo­tor neu­rons – nerve cells that send sig­nals from the spi­nal cord to mus­cles – pro­duce too lit­tle of what is called sur­viv­al mo­tor neu­ron pro­tein.

The re­search­ers used an al­tered vi­rus to de­liv­er a por­tion of DNA that makes the pro­tein in­to the veins of 1- to 10-day-old mice. The vi­rus in­jected in­to the youngest mice reached al­most half of their mo­tor neu­rons, re­sult­ing in im­proved mus­cle co­ordina­t­ion, prop­erly work­ing elec­tri­cal sig­nals to the mus­cles and long­er sur­viv­al, sci­en­tists said.

“When you put the pro­tein in post­na­tally, it will res­cue the ge­net­ic de­fect,” said Ar­thur Burghes, bio­chem­ist at Ohio State Uni­vers­ity and a sen­ior co-author of the stu­dy. “This tech­nique cor­rects the mice con­sid­erably more than any drug cock­tails be­ing stud­ied as a po­ten­tial treat­ment in hu­mans.”

Gene ther­a­py is a rel­a­tively new class of ex­per­im­en­tal treat­ments in­volv­ing in­tro­duc­ing genes in­to pa­tients through var­i­ous means in or­der to re­place de­fec­tive genes or oth­er­wise help fight ill­ness. Al­though gene ther­a­py has sparked great ex­cite­ment among sci­en­tists, the re­search has suf­fered set­backs, in­clud­ing a 1999 death dur­ing a clin­i­cal tri­al for or­ni­thine tran­scar­boxy­lase de­fi­cien­cy. Oth­er stud­ies have shown better re­sults, but the U.S. Food and Drug Ad­min­istra­t­ion has to date not ap­proved any gene ther­a­py treat­ments. 

Spi­nal mus­cu­lar at­ro­phy is a ge­net­ic dis­or­der that strikes about one in eve­ry 6,000 ba­bies born in the Un­ited States, and leads to death in some af­fect­ed chil­dren be­fore age 2. Ac­cord­ing to the Na­tional In­sti­tutes of Health, there are many types of the dis­or­der, and life ex­pect­an­cy de­pends on how the dis­ease af­fects breath­ing. There is no cure, but medicines and phys­i­cal ther­a­py help treat symp­toms.

The re­search is pub­lished on­line in the jour­nal Na­ture Bi­o­tech­nol­ogy.

The sci­en­tists used a spe­cial form of a vi­rus to de­liv­er the pro­tein to nerve cells in the mice. This vi­rus still has the ca­pa­bil­ity to in­fect cells but has been al­tered so it will not copy it­self and cause ill­ness in hu­mans, said Bri­an Kas­par, an in­ves­ti­ga­tor in the Re­search In­sti­tute at Na­tion­wide Chil­dren's Hos­pi­tal and as­sis­tant pro­fes­sor of pe­di­at­rics at Ohio State, al­so a sen­ior co-author of the stu­dy.


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A deadly muscle-wasting disorder that afflicts children may be susceptible to effective treatment through gene therapy, scientists say. Research in mice found that the therapy could reverse a protein deficiency characteristic of the condition and thus correct muscular function, restore nerve signals and improve survival. The mice were engineered to develop that disorder, spinal muscular atrophy, sometimes also called floppy baby syndrome because of its strength-sapping effects. The disease results when due to a missing gene, motor neurons – nerve cells that send signals from the spinal cord to muscles – produce too little of what is called survival motor neuron protein. The researchers used an altered virus to deliver a portion of DNA that makes the protein into the veins of 1- to 10-day-old mice. The virus injected into the youngest mice reached almost half of their motor neurons, resulting in improved muscle coordination, properly working electrical signals to the muscles and longer survival, scientists said. “When you put the protein in postnatally, it will rescue the genetic defect,“ said Arthur Burghes, biochemist at Ohio State University and a senior co-author of the study. “This technique corrects the mice considerably more than any drug cocktails being studied as a potential treatment in humans.“ Gene therapy is a relatively new class of medical treatments involving introducing genes into patients through various means in order to replace defective genes or otherwise help fight illness. Although gene therapy has sparked great excitement among scientists, the research has suffered setbacks, including a 1999 death during a clinical trial for ornithine transcarboxylase deficiency. Other studies have shown more promising results, but the U.S. Food and Drug Administration has to date not approved any gene therapy treatments. Spinal muscular atrophy is a genetic disorder that strikes about one in every 6,000 babies born in the United States, and leads to death in some affected children before age 2. According to the National Institutes of Health, there are many types of the disorder, and life expectancy depends on how the disease affects breathing. There is no cure, but medicines and physical therapy help treat symptoms. The research is published online in the journal Nature Biotechnology. The scientists used a special form of a virus to deliver the SMN protein to nerve cells in the mice. This virus still has the capability to infect cells but has been altered so it will not copy itself and cause illness in humans, said Brian Kaspar, an investigator in the Research Institute at Nationwide Children's Hospital and assistant professor of pediatrics at Ohio State, also a senior co-author of the study.