Tuesday, June 2, 2015

Type 1 Diabetes Reversed in Mice

Type 1 diabetes accounts for about 5% of all diabetes and is usually diagnosed in young people. There is no cure for the disease - which happens when the immune system destroys pancreatic beta cells and the body's only source of insulin, a hormone that controls blood sugar. Now researchers report they have successfully tested a new therapy that appears to reverse new onset type 1 diabetes in mice.
Investigators from the University of Cincinnati (UC) presented their findings at the 74th Scientific Sessions of the American Diabetes Association in San Francisco on 14 June 2014.
There are two parts to the immune system: the innate immune system, which we are born with and attempts to fight infection straight away; and the adaptive immune system, which takes time to mount a response that is more specific to the particular pathogen.
The innate immune system includes a group of cells known as dendritic cells that send messages to the adaptive immune system. Dendritic cells are important antigen processors - they have receptors on their cell surface that react to pathogens and present their antigens to the adaptive immune cells such as immature T cells to develop a more precise response.
Most previous attempts to combat type 1 diabetes have aimed at reducing an overzealous adaptive immune response by eliminating the auto-reactive T cells directly. But in this new study, the researchers used an approach that tackles T cells indirectly, as study leader William Ridgway, a professor in medicine at UC, explains:
"We are targeting a receptor that is found mostly on the innate immune cells, such as dendritic cells."
He and his team decided to tackle a receptor on dendritic cells called TLR4. Previous studies have already established that non-obese diabetic mice have faulty innate immune cells, and that this could be partly due to a defect in TLR4, which many suspect helps to prevent type 1 diabetes when it functions normally.

Antibody that boosts TLR4 reversed new onset type 1 diabetes in mice

The researchers found when they used an agonistic monoclonal antibody, UT18, to boost the activity of TLR4 in mice with new onset type 1 diabetes, it reversed the disease in a high percentage of them.

While the TLR4 pathway in humans is similar to that of mice, there are some differences, so further study is required to see if the treatment will work in humans.
Prof. Ridgway says the cause of the reversal was the "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 points out that the key to reversing type 1 diabetes in the mice was catching the disease right at the onset, which has only a very short time window. The window is likely to be longer in humans, he says, but it is still relatively short before end-stage type 1 diabetes sets in.
While the TLR4 pathway in humans is similar to that of mice, there are some differences, so further study is required to see if the treatment will work in humans.
Prof. Ridgway says there is also a chance, if the therapy works in humans, that it will do so with an agonistic anti-TLR4 agent that is already approved, or under development.
Meanwhile, Medical News Today reported on another study presented at the same conference by researchers from the Intermountain Heart Institute at Intermountain Medical Center in Murray, UT. The Intermountain study explains how type 2 diabetes risk in prediabetics may be combated by periodic fasting to work against the effects of insulin resistance.
Written by Catharine Paddock PhD
source : http://www.medicalnewstoday.com/articles/278289.php

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