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Successful Use of Gene Therapy for Treatment of Type I Diabetes in Dogs
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Dogs are considered human’s best friend, and many pet owners are willing to go to extreme lengths to take care of their companions and provide medical care. Gene therapy has become a popular treatment option for veterinary medicine. In dogs, one of the main conditions treated is osteoarthritis. The gene therapy treatments have helped ease pain and improve quality of life for many pets. Even though many companion animals have benefitted from the results of gene therapy, there have been few scientific studies performed assessing the therapy. However, a recent study has shown successful maintenance of blood glucose levels in dogs with Type I diabetes mellitus.

Researchers from the Universitat Autonoma de Barcelona in Spain had previously demonstrated efficacy of gene therapy treatments in mice with diabetes. However, being able to demonstrate similar efficacy in an large animal, such as dogs, is a big step in moving from pre-clinical mouse studies to clinical trials in humans. Because of differences in body size and life span, it can be difficult to directly correlate results found in mice to humans. Large animal studies can be a good predictor of the potential success of gene therapy in humans. For example, a previous study in dogs that showed promising results for treating hemophilia has been successfully adapted to humans. The long life span of dogs compared to mice also allows researchers to determine potential long term effects of the therapy before moving into clinical trials.

The scientists used an attenuated adenovirus vector to transport genes expressing insulin, a protein that helps cells take in sugar from the blood stream, and glucokinase, a protein that helps increase and decrease insulin production in response to blood glucose levels. The genes were inserted into skeletal muscle cells. Because skeletal muscle cells do not replicate, the genes remain in the cell long term, and the proteins are expressed consistently at low, but effective levels. The gene therapy was efficacious in dogs for as many as four years, which indicate that humans could also be treated long term by the transfer of insulin and glucokinase genes into skeletal muscle cells. The researchers did note that both proteins were required for the dogs to maintain proper blood sugar levels.

The next step for the researchers will be to perform clinical testing in companion animals. All of the dogs used in the study were beagles, and were maintained in a lab. Companion animals will have greater genetic variation, representing more breeds. These clinical studies using companion animals will help determine if gene therapy transplantation of insulin and glucokinase can be effective in a larger variety of dogs. If these trials are successful, the treatment could potentially be translated into humans. While gene therapy would not be a cure for Type 1 diabetes mellitus in dogs or humans, it would provide a long term treatment. Proper glucose levels are important in a diabetic patient, as consistently high levels can cause kidney damage, neuropathy, and other problems associated with diabetes.

While the studies in dogs have demonstrated that insulin and glucokinase genes can help control blood sugar in patients with diabetes, the actually treatment may need to be altered before being used in humans. The vector used to help insert the genes was an attenuated adenovirus. Adenovirus is a causative agent of the common cold. This means that patients may have previously developed immunity against the vector. If a patient is already immune to the vector, his or her immune system would attack and kill the virus before it is able to insert the genes into the cells. In addition, if follow up therapy is needed, a patient would have a high likelihood of having developed immunity against the vector during the primary therapy. This would cause difficulties with follow up injections of the virus. Another problem with using a viral vector to insert genes is that the insertion may occur in random locations. This could cause mutations in the cells, and lead to cancer. While the transfer of insulin and glucokinase genes may indeed be a method to control blood glucose levels in patients with Type I diabetes mellitus, the method of transferring these genes into the patient will likely require more research.


References:

http://www.nbcnews.com/id/51635817#.UX6HckqGY4J
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Successful Use of Gene Therapy for Treatment of Type I Diabetes in Dogs - by bridgettpayseur - 05-02-2013, 07:29 AM
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