A pill staved off type 1 diabetes in mice, and it may one day prevent the disease in people, too.
The pill blocks the buildup of a specific acid in the pancreas, which then stops the disorder from taking hold, according to research published this week in the Journal of Clinical Investigation. Doctors could screen patients for traces of the disorder, and give the medication to those at risk of developing the condition. The pill would then save the body from getting significantly hurt.
"Instead of taking insulin for the rest of your life, it’d just be a pill, and you wouldn’t get diabetes."
Type 1 diabetes is an autoimmune disorder that shuts down the body’s production of insulin. Normally, insulin is made by beta cells in the pancreas; it's a hormone that's important for converting the sugars we eat into energy. But for patients with type 1 diabetes, the body's immune system destroys the pancreatic beta cells, effectively halting insulin production. The condition is different from type 2 diabetes, where the body doesn’t produce enough insulin or the insulin stops working properly. Type 1 diabetes, usually diagnosed during childhood or adolescence, affects more than 1.25 million Americans.
Patients with type 1 diabetes must regularly inject themselves with insulin for the rest of their lives in order to control the amount of sugar in their blood. Otherwise, too much blood sugar can wreak havoc on their bodily systems. But if the disorder never takes hold, then there’s no longer a need for lifelong shots. "Instead of taking insulin for the rest of your life, it’d just be a pill, and you wouldn’t get diabetes," Dr. Paul Bollyky, a professor of infectious disease at Stanford, told The Verge.
The idea sprang from analyzing what happens in the pancreas before it stops producing insulin. This has been incredibly difficult for scientists to do, since pancreatic tissues can only be studied after a person dies. "You can’t biopsy the pancreas," said Bollyky. "By the time you can look in the tissues, it's after people die, so you're years to decades out from what happened as far as when the disease started to form."
To get around this, the researchers used pancreatic tissues from people who had died right after being diagnosed with type 1 diabetes. The patients had donated their organs to the Juvenile Diabetes Research Foundation. This collection of pancreases helped the team see what was going on in the early stages of the disorder. The pancreases had a significant buildup of something called hyaluronic acid, which is often found in areas of inflammation. And the build-up was most notable near the pancreatic beta cells — the ones that make insulin.
This image shows a mouse's pancreatic cells, which have produced insulin (stained brown). The mouse, which was engineered to develop type 1 diabetes, was treated with hymecromone for seven weeks. (JCI)
This buildup may be helping the immune system do extra damage to the pancreas, Bollyky says. Hyaluronic acid is instrumental in causing sites to swell; it soaks up water and increases fluid buildup. It also makes inflammation worse by suppressing the body's regulatory T cells, which help to keep the immune system in check. "Think of your immune system as an army, and the regulatory T cells are the military police," said Bollyky. "If a marauding army conquers a new area, there's lots of pillaging going on afterward, so you need military police to keep that from happening. They rein in the army and make them behave."
But without the regulatory T cells, the immune system can damage otherwise healthy cells. Bollyky thinks the hyaluronic acid is preventing the regulatory T cells from showing up in the pancreas, so the immune system isn’t being told to stand down from a person’s own body. The Stanford researchers wondered if getting rid of the hyaluronic acid would allow the regulatory T cells to restore balance
So they turned to a drug called hymecromone, which is already used in Europe and Asia to treat complications associated with gallstones. It also has the side effect of shutting down hyaluronic acid production. The researchers tested out hymecromone's abilities by giving it to mice that had immune systems engineered to attack the pancreatic beta cells.
Hymecromone may be safe for use overseas, but it hasn't been approved yet by the FDA.
In the mice taking the drug, the regulatory T cells showed up in the pancreas and subdued the overactive immune response. The immune cells still stayed in the pancreas, but they didn't touch the beta cells. "The invading army doesn’t go anywhere, but all of a sudden it becomes respectful," said Bollyky. "It's respectful inflammation that's not destroying your beta cells anymore."
Perhaps the biggest hurdle the researchers have to overcome is showing the drug works the same in humans. Bollyky says they’re moving on to human clinical trials soon. But only a small percentage of drugs make receive full FDA approval. Only a third of drugs that enter the second stage of clinical testing typically required by US regulators move on to final stage. Bollyky says he’s confident that the drug will at least be considered safe, since it’s already used abroad. However, rodents and humans aren’t the same, so what works for one animal may not work for the other.
And then there's still a lot of work to be done before people can start using this drug to treat diabetes. While hymecromone may be safe for use overseas, it hasn't been approved yet by the U.S. Food and Drug Administration. Additionally, Bollyky wants to rework the drug so that it's something patients can take once a week. Right now, to match the mouse dosing schedule, they would have to take it multiple times a day. They’d also have to take the pill for the rest of their lives, though it might spare them insulin injections, which are a major cause of emergency room visits.