Gene Therapy Restores Blood Sugar Control to Near Normal
Nov. 22, 2000 -- Using a new form of gene therapy, researchers in South Korea and Canada have tricked the liver into producing a substance like insulin to replace the insulin the pancreas can't produce, resulting in long-term control of blood sugar in animals with a form of type 1 diabetes. If successful in humans, the technique, described in the Nov. 23 issue of the journal Nature,could enhance or perhaps replace the need for insulin injections.
Type 1 diabetes, in the past referred to as juvenile-onset or insulin-dependent diabetes, for the majority of people is caused when the body turns on itself and directs the immune system to attack and destroy cells in the pancreas that produce insulin. The cells, called beta-islet cells, produce insulin, a hormone that is necessary for the regulation of glucose, the primary blood sugar used by the body for energy. Because their bodies can no longer produce the insulin they need, people with type 1 diabetes must inject themselves with insulin to keep blood sugar under control.
The experimental therapy uses a specially modified virus to carry into liver cells a gene that senses glucose levels in the blood, coupled with a gene that will cause the liver cells to produce a modified form of insulin that the body can readily use.
When the gene package was injected into the livers of rats with a chemically induced type of diabetes and into mice with a hereditary form of the disease, blood glucose levels returned to normal within two weeks of treatment, and have remained normal for more than five months in mice and more than eight months in rats. The treated animals have shown no apparent side effects from the treatment, report Ji-Won Yoon, PhD, and associates at the University of Calgary in Alberta, and at Yonsei University Medical School in Seoul.
"One of the significant findings of our study is that the liver cells producing [the modified insulin] now take over the function of insulin-producing beta cells, which have been completely destroyed by the autoimmune attack in the mice," Yoon comments in a written statement. But because the new insulin-producing cells are different from beta cells, they are apparently protected from immune system attacks, Yoon says.
Several research teams in Asia, Europe, and North America are working on gene therapy strategies for promoting long-term insulin production in the liver to treat type 1 diabetes. One of the barriers to this form of therapy, however, is that once you've turned on production of insulin, you have to find a way to turn it off to avoid the problems associated with hypoglycemia, a condition caused by extremely low blood sugar levels, which can cause loss of consciousness, diabetic comas, and in extreme cases, death.