June 16, 2014
New Method Of Reversing Type 1 Diabetes In Mice Could Eventually Help Humans
redOrbit Staff & Wire Reports - Your Universe Online
A team of University of Cincinnati researchers has reportedly discovered a way to reverse new onset Type 1 diabetes in mouse models, and their efforts could eventually be used to help humans coping with the disease.
Lead researcher Dr. William Ridgway, director of the university’s division of immunology, allergy and rheumatology, and his colleagues used an agonistic monoclonal antibody known as UT18 to boost the activity of a toll-like receptor that can help prevent the disease.
By doing so, they were able to reverse Type 1 diabetes in a high percentage of newly diabetic non-obese mice, Dr. Ridgway’s team explained in findings presented Saturday during the American Diabetes Association's 74th Scientific Sessions in San Francisco.
Type 1 diabetes is typically diagnosed in children and young adults, and approximately five percent of all people with diabetes are affected by the condition, according to the American Diabetes Association. People who have the disease are physically unable to produce enough insulin to properly metabolize glucose, causing their blood sugar to rise.
Symptoms of Type 1 diabetes include frequent urination, excessive thirst and weight loss, even in those who find themselves eating more. There is currently no cure for the disease, and the incidence rate of Type 1 diabetes and autoimmunity in general has experienced a rapid increase since the middle of the 20th century.
One possible reason for this phenomenon is the fact that the immune systems responsible for providing autoimmunity in kids and young adults are being under-stimulated. Type 1 diabetes causes a person’s own T-cells to attack the insulin-producing beta cells, according to Dr. Ridgway and his colleagues.
“Previously, it has been reported that non-obese diabetic mice have defects in innate immune cells and that TLR4, a toll-like receptor, plays a protective role in preventing Type 1 diabetes,” the university explained in a statement. Based on that knowledge, the researchers successfully used UT18 to boost TLR4’s activity.
“We have shown that by using an antibody to stimulate a specific molecule in the innate immune system we can reverse – with a high rate of success – new onset diabetes in mice that have already developed the symptoms of diabetes,” added Dr. Ridgway. “The cause of this reversal is a preservation of the endocrine pancreatic beta cells that produce insulin. These cells are preserved from the autoimmune attack which is the hallmark of Type 1 diabetes.”
He emphasized that it is essential to catch Type 1 diabetes at its onset in mice in order to reverse it. This gives the scientists very little time to act, and even though the window would be longer in humans, there is still a relatively short period of time from the onset of the disease until its final stages, Dr. Ridgway noted.
His team’s approach is different from other methods of treating Type 1 diabetes because there is no direct interaction with the T-cells of the mice, he continued. Often times, treating autoimmunity focuses on suppressing overactive adaptive immune response by eliminating auto-reactive T-cells, the UC professor added.
“We are targeting a different part of the immune system,” said Dr. Ridgway. “There are two arms of the immune system. One is called the adaptive immune system and the other is the innate immune system. Basically the T-cells and B-cells are in your adaptive immune system and they respond to many different antigens.”
“The innate system tends to have a stereotypical response. We are targeting a receptor that is found mostly on the innate immune cells, such as dendritic cells,” he added. “This same molecular TLR4 pathway operates in humans in many similar ways; though there are some differences, it is possible this new pathway of targeting the immune system could be tested in humans.”
While additional research is necessary to fully investigate the approach, Dr. Ridgway said that the therapy is promising because the US Food and Drug Administration (FDA) has already approved one agonistic anti-TLR4 agent, and that the development of other similar treatments is currently underway.