Type 1 diabetes cure? It seems to have worked for 1 man
Brian Shelton’s life was ruled by Type 1 diabetes.
When his blood sugar plummeted, he would lose consciousness without warning. He crashed his motorcycle into a wall. He passed out in a customer’s yard while delivering mail. Following that episode, his supervisor told him to retire, after a quarter century in the Postal Service. He was 57.
His ex-wife, Cindy Shelton, took him into her home in Elyria, Ohio. “I was afraid to leave him alone all day,” she said.
Early this year, she spotted a call 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 vowed to find a cure after his baby son and then his teenage daughter got the devastating disease.
Brian Shelton was the first patient. On June 29, he got an infusion of cells, grown from stem cells but just like the insulin-producing pancreas cells his body lacked. Now his body automatically controls its insulin and blood sugar levels.
Shelton, now 64, may be the first person cured of the disease with a new treatment that has experts daring to hope that help may be coming for many of the 1.5 million Americans suffering from Type 1 diabetes.
“It’s a whole new life,” Shelton said. “It’s like a miracle.”
Diabetes experts were astonished but urged caution. The study is continuing and will take five years, involving 17 people with severe cases of Type 1 diabetes. It is not intended as a treatment for the more common Type 2 diabetes.
“We’ve been looking for something like this to happen literally for decades,” said Dr. Irl Hirsch, a diabetes expert at the University of Washington who was not involved in the research. He wants to see the result, not yet published in a peer-reviewed journal, replicated in many more people. He also wants to know if there will be unanticipated adverse effects and if the cells will last for a lifetime or if the treatment would have to be repeated.
But, he said, “Bottom line, it is an amazing result.” Dr. Peter Butler, a diabetes expert at UCLA who also was not involved with the research, agreed while offering the same caveats.
“It is a remarkable result,” Butler said. “To be able to reverse diabetes by giving them back the cells they are missing is comparable to the miracle when insulin was first available 100 years ago.” And it all started with the 30-year quest of a Harvard University biologist, Doug Melton.
A terrible disease
Melton never had thought much about diabetes until 1991 when his 6-month-old boy, Sam, began shaking, vomiting and panting.
“He was so sick, and the pediatrician didn’t know what it was,” Melton said. He and his wife, Gail O’Keefe, rushed their baby to Boston Children’s Hospital. Sam’s urine was brimming with sugar — a sign of diabetes.
The disease, which occurs when the body’s immune system destroys the insulin-secreting islet cells of the pancreas, often starts around age 13 or 14. Unlike the more common and milder Type 2 diabetes, Type 1 is quickly lethal unless patients get injections of insulin. No one spontaneously gets better.
“It’s a terrible, terrible disease,” said Butler at UCLA. The only cure that has ever worked is a pancreas transplant or a transplant of the insulin-producing cell clusters of the pancreas, known as islet cells, from an organ donor’s pancreas. But a shortage of organs makes such an approach an impossibility for the vast majority with the disease.
“Even if we were in utopia, we would never have enough pancreases,” said Dr. Ali Naji, a transplant surgeon at the University of Pennsylvania who pioneered islet cell transplants and is now a principal investigator for the trial that treated Shelton.
Blue clues
Melton had been studying frog development but abandoned that work, determined to find a cure for diabetes. He turned to embryonic stem cells, which have the potential to become any cell in the body. His goal was to turn them into islet cells to treat patients.
The challenge was figure out what sequence of chemical messages would turn stem cells into insulin-secreting islet cells. After years when nothing worked, a small team of researchers, including Felicia Pagliuca, a postdoctoral researcher, was in the lab one night in 2014, doing one more experiment.
“We weren’t very optimistic,” she said. They had put a dye into the liquid where the stem cells were growing. The liquid would turn blue if the cells made insulin. Her husband had already called asking when was she coming home. Then she saw a faint blue tinge that got darker and darker. She and the others were ecstatic. For the first time, they had made functioning pancreatic islet cells from embryonic stem cells.
The next step for Melton, knowing he’d need more resources to make a drug that could get to market, was starting a company.
Moments of truth
His company Semma was founded in 2014.
One challenge was to figure out how to grow islet cells in large quantities with a method others could repeat. That took five years.
The company, led by Bastiano Sanna, a cell and gene therapy expert, tested its cells in mice and rats, showing they functioned well and cured diabetes in rodents.
At that point, the next step — a clinical trial in patients — needed a large, well financed and experienced company with hundreds of employees. Everything had to be done to the exacting standards of the Food and Drug Administration — thousands of pages of documents prepared, and clinical trials planned.
Chance intervened. In April 2019, at a meeting at Massachusetts General Hospital, Melton ran into a former colleague, Dr. David Altshuler, who had been a professor of genetics and medicine at Harvard and the deputy director of the Broad Institute. Over lunch, Altshuler, who had become the chief scientific officer at Vertex Pharmaceuticals, asked Melton what was new.
Melton took out a small glass vial with a bright purple pellet at the bottom.
“These are islet cells that we made at Semma,” he told Altshuler.
Vertex focuses on human diseases whose biology is understood. “I think there might be an opportunity,” Altshuler told him.
Meetings followed and eight weeks later, Vertex acquired Semma for $950 million. Less than two years after Semma was acquired, the FDA allowed Vertex to begin a clinical trial.