Scientists at Baylor College of Medicine have developed a gene therapy that causes liver cells to convert into insulin producing beta cells which normally are found only in Islets of Langerham in the Pancreas.
HOUSTON (April 21, 2003) – A gene therapy developed by researchers at Baylor College of Medicine has apparently cured diabetes in mice by inducing cells in the liver to become beta cells that produce insulin and three other hormones.
"It's a proof of principle," said Dr. Lawrence Chan, professor of medicine and molecular and cellular biology as well as chief of the division of diabetes, endocrinology and metabolism at the College. "The exciting part of it is that mice with diabetes are 'cured.' "
In the research, which is described in a report in Nature Medicine's online edition today, Chan and his colleagues used the NeuroD gene, a transcription factor that induces the liver to produce cells that make insulin and the three hormones associated with the pancreas' endocrine system.
The gene was attached to a so-called "gutless" adenovirus from which all toxic genes had been removed. This viral vector is a very efficient way to introduce genes into liver cells. Alone, NeuroD partially corrected the disease in the diabetic mice. Combined with a beta cell growth factor called Btc, the gene therapy complete cured the mice's diabetes for at least four months.
An added benefit is that the cells in the liver also produce glucagon, somostatin and pancreatic polypeptide, which may play a role in controlling insulin production and release.
"Until now it has not been possible to induce the formation of islets by any gene therapy approach," said Chan.
It does not mean that the treatment can be used in people immediately.
"It's farther from people than I would like," he said. He knows of no stumbling blocks to its effectiveness in people.
The main stumbling block is the vector or virus used to take the gene into the cells. Chan and his colleagues used the safest viral vector available today, but he expects even safer ones to be available within the decade.
"We want to use the safest vector possible," he said.
The treatment has advantages over transplant of islet cells, the insulin producers in the pancreas, because it avoids the lifelong use of powerful immunosuppressive drugs and eliminates the need to find a compatible donor.
Chan credits one of his postdoctoral students, Dr. Hideto Kojima, with much of the work in developing this protocol.
A UPI article about this report says this treatment does not permanently cure diabetes.
However, this "cure" is temporary and would require repeated injections, researchers point out. Also, just because this worked very well in mice does not guarantee such effects in people. "Unfortunately, it will probably take years," before such a treatment would be available to diabetes patients, Chan said. "Like any other gene therapy, the major concern is safety. People are quite different than mice.
The UPI article is the only article on this story that makes this claim that treatment does not last indefinitely. It seems odd. If cells are induced to differentiate into a different cell type I'd expect the new cell type state to be stable. Also, this treatment has already worked for 4 months in these mice. How long does it take for the treatment to wear off? It is possible that the NeuroD genes added to cells gradually break down and when they stop being expressed then all the downstream effects they cause in the cells stop happening.
Even if the injections had to be periodically repeated they'd still be an enormous boon for sufferers of Type I diabetes. Not only would diabetics be freed from daily injections, blood tests, and carefully regimented diets but they'd also live longer and healthier lives.
In the longer run gene therapies will improve to allow genes to be added to cells in ways that cause those genes to stay around permanently. Ways will be developed to deliver stable plasmids into cells and those stable plasmids will carry the desired genes.
My guess is that within 10 to 15 years type I diabetes will be a curable disease. If the genes used in this latest work have the same effect on human liver cells then the biggest remaining obstacle will be the development of better gene therapy vectors to deliver genes safely into cells. That's a topic that is seeing a great deal of work and it seems reasonable to expect better and safer gene therapy delivery methods will be developed within several years.
|Share |||Randall Parker, 2003 April 21 10:55 AM Biotech Therapies|