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Gene therapy shows promise as hemophilia treatment in animalstudies by ferujkll sdff

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Gene therapy shows promise as hemophilia treatment in animalstudies by
Article Posted: 09/11/2012
Article Views: 87
Articles Written: 2023
Word Count: 519
Article Votes: 0
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Gene therapy shows promise as hemophilia treatment in animalstudies

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For the first time, researchers have combined gene therapy and stem cell transplantation to successfully reverse the severe, cripplingbleeding disorder hemophilia A in large animals, opening the door to the development of newtherapies for human patients. Researchers at Wake Forest Baptist Medical Center's Institute forRegenerative Medicine, collaborating with other institutions,report in Experimental Hematology that a single injection ofgenetically-modified adult stem cells in two sheep converted thesevere disorder to a milder form. The journal is a publication ofthe Society for Hematology and Stem Cells "A new approach to treating severe hemophilia is desperatelyneeded," said lead author Christopher D. Porada, Ph.D., associateprofessor of regenerative medicine at Wake Forest Baptist.

"About75 percent of the world doesn't have access to the currenttreatment therapy to replace missing clotting factors. This putspatients in most of the world at risk of severe and permanentdisabilities." Porada cautioned that challenges will need to be overcome beforethe treatment can be applied to humans, including that the sheepdeveloped an immune response to the therapy that could decrease itseffectiveness and duration. There is currently no cure for the rare bleeding disorderhemophilia. People with this genetic disorder lack a protein, knownas a clotting factor, needed for normal blood clotting.

As aresult, they may bleed for a longer time than others after aninjury, as well as bleed internally, especially in joints such asthe knees, ankles, and elbows. This bleeding can damage the organsand tissues and be life threatening. Even when life-threateningbleeds are prevented with replacement therapy, it doesn't preventsmaller bleeds within the joints that can cause pain and decreasedmobility. People with hemophilia A, the most common type, are missingclotting factor VIII. For the study, the researchers used acombined stem cell/gene therapy approach to increase levels offactor VIII produced by the animals.

The scientists first inserted a gene for factor VIII intoengineered mesenchymal stem cells, a type of adult stem cell. Thecells acting as a carrier for the gene were then injected into theabdominal cavity of the sheep. The scientists selected mesenchymalstem cells to carry the gene because they have the ability tomigrate to sites of injury or inflammation. In the treated animals, the cells migrated to the joints andstopped ongoing bleeding. In addition, all spontaneous bleedingevents ceased, and the existing joint damage was completelyreversed, restoring normal posture and gait to these crippledanimals, and enabling them to resume a normal activity level.

However, a paradox of the treatment was that while the symptomswere eliminated, the sheep developed an immune response to factorVIII, suggesting that the treatment's effects would be reduced orshorter in duration. The scientists are currently working to learnwhy the immune response occurred and to develop strategies toprevent it. "While preliminary, these findings could pave the way for a newtherapy for hemophilia patients who experience debilitatingbleeding in their joints," Porada said. The research was supportedby the National Institutes of Health.

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