By giving mice a drug before they developed symptoms of type 1 diabetes, researchers were able to prevent the animals from developing the disease.
Extreme thirst, frequent urination, lack of energy, even unconsciousness — the warning signs of type 1 diabetes can be severe.
But underneath it all, the mechanisms that cause the body to attack its own insulin-making cells in the pancreas have been a mystery.
“For the longest time, we really haven’t known what’s happened in that tissue during autoimmune diabetes,” Dr. Paul Bollyky, Ph.D., an assistant professor of infectious diseases at Stanford University School of Medicine, told Healthline.
In a new study, published today in the Journal of Clinical Investigation, Bollyky and his colleagues have provided a better view of what goes on in the pancreas during type 1 diabetes.
At the same time, they have identified a potential way to prevent this lifelong disease — provided the drug used in the study proves as successful in people as it did in mice.
In type 1 diabetes, the immune system mistakenly attacks the body’s own cells. In this case, it’s the beta cells of the pancreas, an organ located behind the lower part of the stomach.
Beta cells are found, along with other types of cells, in clusters called islets. The beta cells make insulin, which allows the body to regulate its use of glucose.
Before symptoms of type 1 diabetes develop, certain immune cells migrate to the islets. At first, the migrating immune cells sit near the islets without causing any damage.
At some point they start to attack the beta cells. The reasons for this shift are not entirely known. However, once the attack starts, it keeps going.
Eventually, enough insulin-producing beta cells are destroyed for the symptoms of type 1 diabetes to appear, including high blood sugar levels.
In this study, researchers identified a substance that is essential for the progression from immune cell infiltration to full-blown type 1 diabetes.
The substance first caught their attention during an earlier study, which involved examining pancreatic tissues donated to a tissue bank set up by the Juvenile Diabetes Research Foundation.
“We looked at these tissues from human cadaveric donors,” said Bollyky, “and found that in recent-onset type 1 diabetic patients, they had this molecule called hyaluronan that was around their islets, at places where their immune system was attacking their islets.”
In the new study, the pancreatic tissue of mice that developed type 1 diabetes looked similar to the human tissue bank samples.
“It turns out that [the mice] get the same thing. They have this hyaluronan at sites of autoimmune attack,” said Bollyky. “That’s what really gave us the idea of targeting that molecule — targeting hyaluronan — to see if we can prevent the autoimmunity.”
The presence of hyaluronan near the islets is not enough to confirm its role in type 1 diabetes. For that, the researchers needed to show that blocking the effects of hyaluronan could stop type 1 diabetes in its tracks.
To accomplish this, researchers turned to a drug called hymecromone, or 4-methylumbelliferone (4-MU for short), which is known to block the production of hyaluronan in the body.
This drug is already prescribed in European and Asian countries for spasms caused by gallstones, and it is even approved for use in children.
“If this were a court of law and we were trying to convict this molecule of causing — or contributing to — the progression of autoimmune diabetes,” said Bollyky, “what helps you make that conviction is the fact [that] this drug that shuts down hyaluronic acid production basically prevents autoimmune diabetes in two different mouse models.”
One group of mice required only a week of the drug.
The other needed ongoing treatment. If they stopped taking the drug, these mice quickly developed type 1 diabetes.
For this kind of drug to work in people, though, it needs to be given early on in a child’s life — before too many beta cells are damaged.
“You’ve got a window of opportunity where you could potentially make this diagnosis and treat people,” said Bollyky, “and that’s really what we’re trying to do.”
Screening tests are already available that can identify children at risk of developing type 1 diabetes. These are based on autoantibodies in the blood that indicate the immune system is primed to attack the beta cells.
Although one group of mice only needed a short-term treatment, Bollyky envisions that in people “this drug could be given like a maintenance drug, where somebody who is autoantibody positive could take that, and it would prevent them from coming down with diabetes.”
A daily pill for life may seem like a lot, but people with type 1 diabetes already require multiple injections of insulin each day to control their blood sugar level.
Before the drug can be used in people, though, it still needs to be tested in clinical trials and approved by the Food and Drug Administration.
In spite of these regulatory hurdles, Bollyky is optimistic about the drug’s potential.
“It’s a 40-year-old drug and it’s got a very long and, to be honest, boring track record, in terms of complications and side effects,” said Bollyky, “which is to say, it doesn’t cause many.”