Heads were raised in January when an ambitious California-based diabetes research facility said it was planning to cure type 1 diabetes within six years. The C-word is controversial within diabetes circles, yet the City of Hope had no reticence about making the claim.
Dr Bart Roep is the director of this program at the City of Hope’s Diabetes and Metabolism Research Institute. Born in the Netherlands, he leads a team whose mission is to cure type 1 diabetes, and while their ambitions are lofty, so is their early success.
In March, Dr Roep’s team published the results of a 14-year-boy with type 1 diabetes who underwent stem cell transplantation. The boy has since been free from insulin without any side effects for eight years.
This, De Roep said, was the first definitive proof that type 1 diabetes can be cured. But there are still several critical questions to be answered.
How far away are we from patients receiving transplants and not requiring immunosuppressant drugs? Why do some people respond better to transplantation than others?
We posed these questions and many more to Dr Roep, who spoke to Diabetes.co.uk about whether he regrets the ‘six-year deadline’ claim and how close his research team actually is to curing type 1 diabetes.
“A dangerous word to use”
Dr Roep acknowledges that cure is “a dangerous word to use” in regard to type 1 diabetes research. Thanks to years of media misinformation and fake diabetes cures, there is scepticism within the diabetes community about the legitimacy of the C-word.
But it is a word that features heavily in Dr Roep’s diction. He is not afraid of being bold with his claims, which stems from the confidence in his team’s work.
“What we are trying to do is understand why people get type 1 diabetes and to translate this to find a cure,” Roep said. “That is, of course, a dangerous word to use. But we think that we are onto a couple of leads.”
One of these leads is islet cell transplantation, a procedure that involves transplanting islet (insulin-producing) cells into patients from donor pancreases. In some cases, the transplants can help a patient come off insulin, but other times the cells are rejected or attacked by the immune system unless immunosuppressant drugs are also give, which can cause side effects.
Dr Roep had already spoken of his aim to cure type 1 diabetes within six years prior to the publication of his most recent study.
“Well, announcing the six-year deadline is of course the worst thing you can ever do!” he said. “But, seriously, I wouldn’t have said it if I did not know we were to publish a paper six weeks ago where we actually cured a patient with type 1 diabetes.
“This was a 14-year-old boy when he was treated; he’s now 23 and still doesn’t need a shot of insulin.”
However, the patients in this study were all given immunosuppressant drugs before transplantatio, which renders the operation considerably risky given those aforementioned side effects, which include an increased risk of infection.
But Dr Roep’s team made a significant discovery along the way: by reading the immune signatures of patients they were able to predict how successful transplantation would be. Dr Roep says this is the first step towards personalising medicine in type 1 diabetes.
“It turns out we can predict before surgery who has a fantastic chance of lasting benefit, by which I mean cured for three full years from type 1 diabetes without any additional therapy.
“We found those patients with that immune signature could be treated, however we found another signature that showed a third had no benefit at all. In other words we can now get a complete prediction of who will get the ultimate benefit – complete remission – and those who won’t.”
So why are some patients lucky, and others aren’t? Roep explains:
“This has to do with the rate of islet autoimmunity: how many immune cells patients carried in their blood that were reactive against the cells that made insulin. Using this you can make a triage; you can say that up to half the patients will have very poor benefit, so let’s not do the procedure.
“This is something now that we can use to assign personalised therapy to patients.”
But the pesky problem of immunosuppressant drugs still exists, and Roep acknowledges that because of this there is a long road ahead before transplantation is ‘ready for the big stage’.
“It turns out we can predict before surgery who has a fantastic chance of lasting benefit, by which I mean cured for three full years from type 1 diabetes without any additional therapy.
“The problem with the medication we’re giving now is that these drugs are great at preventing something new but they’re pretty lousy at reversing something that was already there,” said Dr Roep.
“So the problem is that we are using the wrong drugs. The drugs we’re using to prevent rejection of islets induce insulin resistance and type 2 diabetes.
“There are alternatives – people have been working for decades on encapsulation – but there is still a long way to go because the islets need to be able to respond very quickly, so the treatment is not ready yet for the big stage.”
Type 1 diabetes vaccine
Roep’s team is also working on a separate approach: a type 1 diabetes vaccine.
Last year they administered a patient with a vaccine consisting of the patient’s own immune cells, taken from his blood, that were treated with vitamin D3 and a beta-cell protein. Another eight people have since received the vaccine, and an 18-month study period is underway.
Roep is excited about the study because, he says, researchers can now tackle the root cause of type 1 diabetes, whereas before they were only able to treat symptoms.
In February, he proposed that type 1 diabetes results from a mistake of beta cells, not the immune system, an alternative theory to how the autoimmune disease develops.
With this in mind, Roep believes the findings from their new vaccine study could prove significant in correcting the autoimmune response from these beta cells.
“I want to take advantage of the new insight that we have into type 1 diabetes, and that’s the diagnosis,” he said.
“We get told in textbook medicine that you get diagnosed with 90% of beta cells destroyed and the other 10% follow suit, but that’s not true. As a matter of fact, the majority of [type 1] patients have beta cells so that increases the sense of urgency to protect those beta cells, and also to get a better picture of predicting when they will be destroyed.”
Is a cure actually near?
Dr Roep is confident that a cure is indeed on the horizon.
“These are very important times and while I’m not afraid to say cure, I’m a little more reluctant to use time frames.”
He admits that there is still colossal work to be done, but the tools are in place to achieve it. There will be setbacks along the way, but he insists these can help teach scientists more about how best to personalise medicine and future treatments.
“Understanding why [a treatment] sometimes fails will allow us to design new treatment strategies for less fortunate patients.
“We’ve come to learn that type 1 diabetes is heterogeneous as a disease and we should not expect a single medicine to cure it. That’s why we are trying to read the immune signatures of [patients] and translate that to the most appropriate therapies.”
With each generation passing, type 1 diabetes research evolves – it’s been 25 years since the launch of the first insulin pen – and while many will always be sceptical and even fearful of raising their hopes at the prospect of a cure, scientists such as Dr Roep are leading the way to ensuring a cure is available in this generation.
Who know where we’ll be in another 25 years?
Picture: YouTube
