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Lucky Dogs Get Shot at Diabetes Cure
Date:2/14/2013

By Serena Gordon
HealthDay Reporter

THURSDAY, Feb. 14 (HealthDay News) -- In news that might one day help humans who struggle with type 1 diabetes every day, Spanish researchers report that a single session of gene therapy injections cured five beagle puppies who had the blood sugar disease.

Even four years later, the dogs showed no signs of diabetes.

"Our data represent the first demonstration of long-term correction of diabetes in a large animal model using gene transfer," the scientists wrote in the Feb. 7 online issue of Diabetes.

However, the dogs all had a chemically induced version of diabetes that's meant to model human type 1 diabetes.

In humans, type 1 diabetes is an autoimmune disease, which means the body's own immune system mistakenly attacks healthy cells as though they were bacteria or viruses.

In the case of type 1 diabetes, the immune system destroys the insulin-producing beta cells located in the pancreas. Insulin is a hormone that's needed to transport glucose into the body's cells to be used as fuel. Glucose is sugar that comes from the carbohydrates you consume. Carbohydrates are nutrients found in a variety of foods, including fruits, vegetables, breads and sweets.

Once the beta cells are destroyed, the body no longer makes insulin (or makes very little of the hormone), and anyone with type 1 diabetes needs insulin injections or an insulin pump for the rest of their lives.

However, insulin needs change constantly, depending on the type and amount of food eaten and level of physical activity. Even emotions can affect insulin levels. Too little insulin can cause high blood sugar levels, while too much insulin can cause low blood sugar levels. Neither condition is healthy and, if severe enough, either can cause death.

In the current study, the researchers developed a gene therapy that served two purposes: one was to sense the amount of glucose in skeletal muscles and the other was to release insulin. This research group had already tested this therapy in mice, where it was found to be successful in controlling blood sugar levels.

To test the therapy, the researchers needed dogs with diabetes. However, the types of diabetes that occur naturally in dogs aren't the same as type 1 diabetes. So, the researchers induced diabetes in a group of beagle puppies between 6 and 12 months old. The dogs were then given daily insulin injections.

The gene therapy involved a single session of numerous injections in the dog's rear legs. The needles used are like those used in human cosmetic procedures.

The dogs quickly got better and maintained normal blood sugar levels without insulin. The researchers continued to measure blood sugar control and the animals' health for more than four years. The dogs stayed healthy, and seem to have no long-term problems from the gene therapy.

Lead researcher Fatima Bosch, director of the Center of Animal Biotechnology and Gene Therapy at the Universitat Autonoma de Barcelona in Spain, said the next step in their research is to test the gene therapy on dogs with naturally occurring diabetes. The dogs will also be pets, so their living conditions and glucose levels will be varied, more closely mimicking what a person with type 1 diabetes would encounter.

Dr. Camillo Ricordi, director of the Diabetes Research Institute and the cell transplant center at the University of Miami, called the new research "an important study, and a remarkable initial finding. But, this is not a type 1 model of diabetes. This is a model where you induce diabetes chemically and you may have residual [beta] cell function."

Ricordi explained that because it's not naturally occurring type 1 diabetes, there's no worry of the immune system destroying the insulin-releasing cells in the muscle. But, in a person with type 1 diabetes, the immune system could still attack and destroy these new cells.

Dr. Massimo Trucco, chief of the division of immunogenics at Children's Hospital of Pittsburgh, said the issue of autoimmunity is an important one. But, of greater concern to him is that while this therapy worked in very controlled conditions -- the dogs' diets and exercise sessions were controlled -- in real-life conditions, this therapy might not work as well.

"Dogs get the food you want them to have. They probably spent most of their time in a cage. But, kids eat what they want and play when they want, meaning their [blood sugar level] varies dramatically. If you inject this therapy into the muscles, the muscle cells don't have the same apparatus to control the insulin levels that beta cells do. This would release insulin too well to give good control, and could cause [low blood sugar levels] when it does release," he said.

Trucco said he doesn't believe this therapy could translate to humans.

"Human beings are not clones of dogs. Beta cells are more complicated than muscle cells. Muscles just can't secrete insulin quickly and efficiently like beta cells do," he said.

But, he added that this was a very well-done gene therapy study that showed that the particular form of gene therapy used in this research appears to be safe for long-term use.

More information

Learn more about gene therapy from the Human Genome Project.

SOURCES: Massimo Trucco, M.D., chief, division of immunogenics, and professor, pediatrics, Children's Hospital of Pittsburgh; Camillo Ricordi, M.D., director, Diabetes Research Institute and the cell transplant center, University of Miami; Fatima Bosch, director, Center of Animal Biotechnology and Gene Therapy, Universitat Autonoma de Barcelona, Spain; Feb. 7, 2013, Diabetes, online


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