ADA 2017: Type 1 highlights (part 1) – Emily Burns
Just last week around 16,000 researchers and healthcare professionals gathered in San Diego for the American Diabetes Associations 77th Scientific Sessions. What was on the agenda for Type 1 research? We’ve got a series of three blogs for you, on the new tech, tackling the biology and preventing complications.
First up, getting to grips with the immune system and the beta cell.
(Note that the research mentioned here hasn’t yet been published and reviewed by the research community).
Can we prevent Type 1?
Putting it off with oral insulin
We heard about the latest TrialNet study, testing if oral insulin can prevent Type 1. The rationale for this is based on an earlier trial, where scientists tested oral insulin in 372 people at high risk of Type 1. It didn’t work, but looking again at the results, they found that the insulin might have delayed onset of Type 1 by around 4-5 years.
Another trial was needed to check if the results were real. The new trial involved 560 people who had ‘stage 1’ Type 1 diabetes, meaning they had at least two antibodies against the pancreas in their blood, but their blood glucose levels were normal. Participants took oral insulin or a placebo capsule every day and were tested for Type 1 every six months. Overall, after seven years, the oral insulin had had no effect on the time taken to develop Type 1.
But there was a group of people in which the onset of Type 1 was delayed by an average of 31 months. They were producing less insulin at the start of the trial, suggesting they maybe had a more ‘active’ form of Type 1. It’s an exciting find, but the team cautioned that more research was needed to work out what this means.
Immune tolerance is a no-go this time
We also saw the results of the DiAPREV-IT trial, testing Alum-Gad as a preventative therapy. GAD is one of the molecules attacked by the immune system, and research is ongoing to see if giving tiny amounts of these molecules could help the immune system to become tolerant.
50 children at high risk of Type 1 took two doses of Alum-GAD or a placebo, and they were followed up for five years. The drug was safe to use, which is good news, but had no effect on Type 1 development. The researchers believe that the future of Type 1 prevention is likely to involve combination therapies, rather than the single therapy tested in this trial.
But we can learn from other autoimmune conditions. There are many drugs licensed for these already, known as immuno-modulatory therapies. Researchers are beginning to ask whether they could be used to treat Type 1.
The main concerns are around safety. You have to be very sure a drug is safe for use in children, and they don’t always have the same effects in children and adults. Immuno-modulatory drugs can also come with side effects, like an increased risk of certain cancers. There are questions as to whether young people should take these drugs for long periods of time, when other options for managing Type 1 are available.
All about the islet
Dr Alice Tomei presented some really interesting research around encapsulation: the idea that you can ‘wrap up’ beta cells to protect them from the immune system. While islet transplants have been revolutionary for some, people still need to take drugs to suppress the immune system and often need more than one transplant. Researchers are looking for coating that will let insulin and waste out, let glucose and nutrients in, and keep immune cells at bay.
A molecule called alginate (derived from algae) has already been shown to protect cells inside a capsule. The problem comes down to size: small capsules slow down insulin release by around two minutes, while large capsules stop the insulin response altogether.
So the size needs to be optimised, preferably coating the outside of the cells rather than creating a ‘capsule’ that they sit within. Dr Tomei is looking at using different molecules to recreate the scaffolding system that usually sits outside of cells, called the extracellular matrix.
They’ve tested this formula and found that the cells carry on working for around seven days. When transplanted into mice, blood glucose levels go back to normal, blood vessels form and the islets survive for at least three months without drugs to suppress the immune system.
Scientists hope to try this new method in people, but they’re not quite there yet. They need to find a way to scale up the production of islets (as donated islets are in scarce supply) and optimise their fake scaffold.
Insulin in the gut?
Finally, we heard from Professor Domenico Accili, who won the ADA’s Banting Award for Scientific Achievement. Professor Accili has found a gene, called FOXO, which is involved in the function of the beta cell. They’ve found that switching FOXO off causes insulin-producing cells to crop up in the gut. Professor Accili believes this could be relevant for future Type 1 therapies and is looking for drugs that can convert intestinal cells into insulin-producing ones.
New drugs on the horizon
The long-awaited insulin pill
There’s one area of research that’s remained out of reach for decades: an oral insulin pill. I mentioned oral insulin earlier in this blog, but that type is broken down in the gut. Researchers are trying to develop insulin that makes it through the gut and into the blood stream in one piece, where it can do its job.
Dr Karsten Wassermann presented the results of the Novo Nordisk study testing their oral insulin in 50 people with Type 2 diabetes who had never taken insulin before. The participants took either oral insulin or insulin glargine for eight weeks, with the results showing that both types improved blood glucose levels in a similar fashion.
“The results of our feasibility study show for the first time time that it’s possible to develop, on a small-scale level, therapeutically meaningful insulin in an easy-to-take oral tablet.” explained Dr Wassermann.
But for now, it’s back to the drawing board for Novo Nordisk. While the results are exciting – and relevant for people with Type 1 and Type 2 diabetes – only around 2 percent of the insulin in the pill was absorbed through the gut, making it very inefficient. Research is now focused on improving the technology to see if it can be made more efficient and therefore more commercially viable.
In people with diabetes, the activity of glucagon (the hormone responsible for increasing blood glucose levels) can go out of balance, making blood glucose levels higher.
Dr Jeremy Pettus’ team found a drug – called REMD-477 – that can block the activity of glucagon, reducing the amount of insulin that people need to take and improving blood glucose levels without causing hypos. They tested the drug in 21 people with Type 1 during a five-day hospital stay and blood glucose levels were then monitored with CGM for eight weeks – with the effects of the drug lasting for this amount of time.
Some animal research has suggested that blocking glucagon activity can promote beta cell formation in the pancreas, but we don’t know if that’s the case in humans yet. A follow-up study will now look at treating more people for longer, and try to understand how REMD-477 works.
That’s it for part one – check out part two and three for more Type 1 ADA news! And there’ll be updates on Type 2 research to follow.