New diabetes trial provides at least temporary cure for small group of severe Type 1 patients

A stem cell trial on a dozen Type 1 diabetes patients suffering from a severe form of the disease has provided at least a temporary cure for 10 participants. The remaining two also dramatically reduced the amount of insulin they require daily.

The treatment, with an infusion called Zimislecel, was created by Vertex Pharmaceuticals and has been the life's work of Boston-based researcher Dr. Douglas Melton, whose stem cell research began at Harvard University. He now works in the stem cell and gene therapy program at Vertex. Melton's interest in "curing" diabetes began more than 25 years ago when his infant son and then adolescent daughter were both diagnosed with Type 1 diabetes.

The recent study was published in the online New England Journal of Medicine and presented at the annual meeting of the American Diabetes Association. Though the study included only 12 patients who suffer from a subset of Type 1 diabetes known as hypoglycemic unawareness, characterized by unexpected and dangerous drops in blood sugar, Melton said that even he was surprised by the success of the infusions, which have allowed most of those patients to live what they call "normal lives," free of insulin and debilitating sugar fluctuations, for the last two years.

One of those patients, Amanda Smith, who was diagnosed at 25 with Type 1 diabetes and hypoglycemic unawareness.

"The cells did their magic after about 6 months," Smith, who lives in Canada, said. "I fully stopped taking all forms of insulin."

Dr. Melton spoke with Here & Now's Robin Young.

When your kids were diagnosed with Type 1 diabetes, did you really say I'm going to cure diabetes? 

"I wouldn't have said that publicly, but I think I told my wife that I thought it was curable, that I thought there were ways that you could try to make cells into insulin-producing cells, and so I was hoping that Sam and Emma wouldn't have to do what you described as injecting themselves and monitoring their sugar all the time."

What's that like for a parent? 

"Well, for a parent, I think it would be best to interview my wife because Gail had to get up every few hours in the middle of the night and prick Sam's finger and squeeze out some blood because, of course, a little baby can't talk, so it was really quite a challenge. As she might have said, she was being his pancreas.

"And so why don't I make myself useful and get back in the lab and try to do something about it?"

You started working with a small team on this stem cell treatment. These stem cells are cells that can morph into different types of cells in the body so they can be sort of a repair system. 

“So, what we had to do is coax them or educate them, to tell them, that we wanted them to become pancreatic islets. There's a cell within the islet called the beta cell that makes insulin. So that was really our goal.

"We tried many things that didn't work, and I give credit to the 50 or more students who worked with me. If you really want to get something done, you have to persist."

What does it mean to be in the trial? 

"People who suffer from Type 1 diabetes have to monitor their blood sugar, their diet, their exercise every day. The people who participate in the trial are patients that, despite their attention to the disease, are unable to control their blood sugar levels.

"They suffer from being unaware of when their blood sugar is so low that they may faint or go into a coma or have a car or motorcycle accident.

"The stem cell-derived islets, which we have a nice name for called Zimislecel, they are injected into the patient's liver because when your pancreas secretes insulin, it goes to the liver.

"So, they receive the cells in their liver along with something called immunosuppressants, which are the drugs that are used in all organ transplants to prevent the host of the patient from rejecting the transplant.  Then after some time, we're delighted to note that these stem cell-derived islets are making insulin, so the patient no longer needs to inject themselves with insulin. They become what's called insulin dependent."

It's not without a risk because anti-rejection drugs they can reduce immunity, people can get infections that can put them at greater risk for cancer.  Are you worried about that? 

"Well, of course we're concerned about that, but Vertex is well known for innovating on and improving the medicines they make, and so we have a number of plans to reduce the immunosuppressants and try other approaches that will allow the cells to survive."

As the data started to come back in when people were saying ‘I'm cured,’ what were you thinking? 

“I would say it worked better than I expected.  I was hoping that the cells we made would produce insulin, but it turns out they control the patient's glucose levels perfectly as far as we can tell. What we're doing is putting in what you might say nature cells, the cells that normally regulate blood sugar. And we're just replacing the missing cells. So, I think that's going to be the most effective way to treat diabetes.

“It's fair to say when I came home and told my two children, there were some tears at the dinner.”

Is it possible that this will be taken to Type 1 diabetics in general, the other 2/3 of that population? Who might this benefit?

"'Can we treat all people with type one diabetes?' The answer is we don't know. One should think about how you might eventually try to do that with cell transplants, but we don't know that at this time."

This interview has been edited for clarity.

Karyn Miller-Medzon produced and edited this interview for broadcast with Todd Mundt. Michael Scotto adapted it for the web.