A possible cure for diabetes? For one man at least it seems to have worked.

When his blood glucose dropped too low, he would suddenly pass out. Brian crashed the motorcycle into a wall. He passed out in the garden of a customer’s house while delivering his mail. After this incident, his supervisor ordered him to retire, after a quarter of a century working for the Post Office. Brian was 57 years old.

His ex-wife, Cindy Shelton, called him to live with her at their home in Elyria, Ohio. “I was afraid to leave him alone all day,” he explained.

A few months ago Cindy saw an invitation for people with type 1 diabetes to participate in a clinical trial by Vertex Pharmaceuticals. The company was testing a treatment developed over decades by a scientist who promised to find a cure after his baby son and teenage daughter developed the devastating disease.

Brian Shelton was the first patient. On June 29 of this year he received an infusion of cells created from stem cells, but exactly the same as the insulin-producing pancreatic cells his body lacked.

Now your body automatically controls your insulin and blood glucose levels.

Brian, who is 64, could be the first person to be cured of type 1 diabetes with a new treatment that is taking experts to risk hoping that help may be on the way for many of the 1.5 million people. Americans who suffer from type 1 diabetes.

“It’s a whole new life,” Brian said. “It’s like a miracle.”

Diabetes experts reacted with amazement but urged caution. The study continues and will take five years, involving 17 people with severe cases of type 1 diabetes. Treatment is not considered for the more common type 2 diabetes.

“We’ve been waiting for something like this to happen literally for decades,” said University of Washington physician Irl Hirsch, a diabetes specialist who was not involved in the research. He wants to see the result, which has not yet been published in a peer-reviewed scientific journal, replicated in many more people. Hirsch also wants to know if there will be unanticipated adverse effects and if the cells will last a lifetime, or if the treatment will need to be repeated.

Still, he said, “ultimately, it’s a fantastic result.”

UCLA physician Peter Butler, a diabetes specialist who was also not involved in the research, agreed with Hirsch and made the same reservations.

“It’s a remarkable result,” said Butler. “Being able to reverse diabetes by giving patients back the cells they lack is comparable to the miracle when insulin was first made available a hundred years ago.”

And it all started with research work carried out over 30 years by a Harvard University biologist, Doug Melton.

“A terrible disease”

Melton had never thought much about diabetes until 1991, when his 6-month-old son, Sam, started shaking, vomiting, and panting.

“He was very sick, and the pediatrician didn’t know what it was,” Melton said. He and his wife, Gail O’Keefe, rushed their baby to Boston Chirldren’s Hospital. Sam’s urine was extremely high in glucose—a symptom of diabetes.

The disease, which occurs when the immune system destroys the pancreatic islets, cells that produce insulin, often starts around 13 or 14 years of age. Unlike type 2 diabetes, which is more common and milder, type 1 diabetes becomes lethal in a short time unless the patient receives insulin injections. Nobody improves spontaneously.

“It’s a terrible, terrible disease,” said Butler of UCLA.

The only cure that has ever worked is a pancreas transplant or a transplant of the pancreas insulin-producing cell clusters, known as pancreatic islets, from a donor pancreas. But the shortage of organs makes this option unfeasible for the vast majority of patients.

“Even if we were in a utopian situation, we would never have enough pancreas,” said Dr. Ali Naji, a transplant surgeon at the University of Pennsylvania. He was the first to perform pancreatic islet transplants and is now the principal investigator of the clinical trial in which Brian Shelton was treated.

blue lanes

For Melton and O’Keefe, caring for a baby with type 1 diabetes was highly frightening. O’Keefe had to prick his son’s fingers and toes four times a day to check his blood glucose. Then I needed to inject him with insulin. Insulin was not even sold in the proper dose for such a small baby. His parents had to dilute the doses.

“Gail told me, ‘If I’m going to have to do this from here, you’re going to have to understand this damn disease,'” Melton recalled. Their daughter, Emma, ​​four years older than Sam, would also later develop the disease, at age 14.

Melton was studying the development of frogs, but he abandoned that work, determined to seek a cure for diabetes. He turned his attention to embryonic stem cells, which have the potential to become any cell in the body. His goal was to convert them into pancreatic islets to treat diabetic patients.

The challenge was to figure out which sequence of chemical messages would convert stem cells into insulin-producing pancreatic islets. This required understanding normal pancreatic development, figuring out how islets are created in the pancreas, and conducting endless experiments to get embryonic stem cells to convert to pancreatic islets. It was a lengthy process.

After years in which nothing went right, one night in 2014 a small team of researchers, including postdoctoral fellow Felicia Pagliuca, was in the laboratory carrying out yet another experiment.

“We weren’t very optimistic,” she said. Scientists had put a dye in the liquid in which the stem cells were growing. The liquid would turn blue if the cells produced insulin.

Pagliuca’s husband had already called to ask when she was going home. Then she saw a very light blue that got darker and darker. She and the other researchers were ecstatic. They had created functional pancreatic islets from embryonic stem cells for the first time.

The lab greeted the advance with a small party and cake. Scientists had bright blue wool berets made with five circles in red, yellow, green, blue and purple, representing the stages that stem cells had to go through to become functional pancreatic islets. They had always rooted for the purple, but until then they had always run aground on the green.

Aware that he would need more resources to produce a drug that could reach the market, the next step for Melton was to start a company.

moments of truth

His company was founded in 2014 under the name Semma, a fusion of his children’s names, Sam and Emma.

One challenge was figuring out how to create large numbers of pancreatic islets with a method that could be replicated by others. This took five years.

Led by specialist in cell therapy and genetics Bastiano Sanna, the company tested the cells it produced in mice and rats, showing that they worked well and cured diabetes in rodents.

At that point, the next step — a clinical trial with human patients — required a large, experienced, well-funded company with hundreds of employees. Everything had to meet the stringent criteria of the US Food and Drug Administration (FDA)—thousands of pages of documents would have to be prepared and many clinical trials planned.

Chance intervened. In April 2019, at a meeting at Massachusetts General Hospital, Melton ran into a former colleague of his, the physician David Altshuler, who had been professor of genetics and medicine at Harvard and deputy director of the Broad Institute. Over lunch, Altshuler, who had become the scientific director of Vertex Pharmaceuticals, asked Melton what his news was.

Melton pulled out a small glass vial with a bright purple ball at the bottom.

“These are pancreatic islets that we created at Semma,” he told Altshuler.

Vertex works with human diseases whose biology is understood. “I think there might be an opportunity,” Altshuler told him.

Meetings followed, and eight weeks later Vertex bought Semma for $950 million. With the acquisition, Sanna became Vertez’s Executive Vice President.

Less than two years after the Semma acquisition, the FDA authorized Vertex to start a clinical trial, with Brian Shelton as its initial patient.

Like patients who receive pancreatic transplants, Brian needs to take medications that suppress his immune system. He says the meds have no side effects and that he finds them far less costly and risky than constantly monitoring his blood glucose and taking insulin. He will have to continue taking the medications to keep his body from rejecting the infused cells.

But diabetes specialist John Buse, at the University of North Carolina and unrelated to Vertex, says immunosuppression makes him think twice. “We need to carefully assess what is riskier: coping with the problems of diabetes or facing the potential complications of immunosuppressive drugs.”

Last month Vertex was ready to reveal the results to Melton. He didn’t expect much.

“I was prepared to have to give them a boost of spirit,” he said.

Normally a calm man, Melton was nervous, anticipating what it looked like would be the moment of truth. He had spent decades and invested all his energies in this project. When the Vertex team presentation ended, a huge smile spread across his face: the data was real.

Melton left Vertex and went home to dinner with Sam, Emma and O’Keefe. When they sat down to eat, he told them about the results.

“Let’s just say there were a lot of tears and hugs,” he said.

For Brian, the moment of truth came a few days after the procedure, when he left the hospital. He measured his blood glucose. It was perfect. He and Cindy had a meal. His blood glucose remained in the normal range.

Brian cried when he saw the numbers.

“The only thing I can say is ‘thank you’.”

Translation by Clara Allain.