The therapy used in the study actually included two different genes: one for glucokinase, an enzyme that acts as a “glucose sensor” in the muscle, and another for insulin, the hormone that causes sugar in the blood to be absorbed into cells to be used for energy. The genes worked in concert to detect high blood sugar levels and then produce insulin to promote the uptake of blood glucose into cells.
The study included five beagles between 6 and 12 months old with type 1 diabetes, which means their pancreases made little or no insulin. Dogs do develop diabetes naturally, but the diabetes cured in this study was chemically induced, after which they began receiving daily injections of insulin. They then received the gene therapy and insulin injections were stopped. After a single administration of the gene combination that included several injections to the hind leg, the dogs’ blood glucose levels were effectively controlled for the over four years that they were monitored. In fact, the therapy was better at controlling their blood glucose levels than daily doses of insulin. Furthermore, their body weights returned to normal and they were generally healthy, lacking any complications from the gene therapy.
A one time gene therapy would be a much welcomed alternative to a lifelong dependence on insulin injections. Type 1 diabetes is thought to be an autoimmune disorder by which the insulin-producing beta cells of the pancreas are attacked by the body’s own immune system. Incapable of producing insulin the body’s blood sugar levels rise, which, left unchecked can wreak havoc on multiple organs and cause heart problems, kidney damage, and nerve damage which can result in blindness. A person with type 1 diabetes needs to receive insulin injections or have an insulin pump to survive.
Although the results are promising, there are some shortcomings to the model. The fact that the type 1 diabetes was not naturally occurring in the dogs and needed to be induced means there could be some surviving, functioning beta cells in the pancreas that weren’t chemically killed off. Likewise, any effective treatment for humans will need to deal with an immune system that is waging constant attack against its own insulin-producing cells. Another of the study’s limitations is the controlled environment in which the dogs were kept. Their regimented diets and amounts of exercise don’t replicate reality – the varied lifestyles of people with diabetes.
Dr. Massimo Trucco, Head of the Division of Immunogenetics at the University of Pittsburgh, isn’t hopeful that the therapy would be effective in humans. “Dogs get the food you want them to have,” he commented in an NIH report of the study. “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.” He also finds fault with the gene strategy. “Beta cells are more complicated than muscle cells. Muscles just can’t secrete insulin quickly and efficiently like beta cells do.”
To address the behavioral concern, Bosch plans on following up the study with one that uses dogs with naturally occurring diabetes and who are also pets. Their voluntary eating and activity patterns will more closely model that of a person with type 1 diabetes.
All studies have their limitations. At the very least the gene therapy’s longterm safety in the current study is an achievement. We’ll just have to wait for future results to find out if the therapy only works in an artificial model in dogs or it holds promise for dogs with naturally occurring diabetes and their diabetic best friends.
