World's first patient cured of diabetes thanks to miraculous stem cells

Brian Shelton is a postman working in the US state of Ohio. At 64 years old, nearly two-thirds of his life has been miserable with type I diabetes. Unlike type II diabetes, which is a common and milder disease, type I diabetes is a constant threat to the patient's life.

It occurs when cells in the pancreas are destroyed by the immune system itself. The patient is therefore unable to produce insulin, a hormone whose job is similar to that of Shelton - a postman who delivers sugar molecules to every cell in the body.

The consequence of not having insulin is that the cells cannot get sugar, which they use as fuel. Patients will therefore have to inject insulin at least twice daily before meals and for the rest of their lives to compensate for what their pancreas cannot produce on its own.

A blood glucose test kit by Brian Shelton, something he must carry with him when he has type I diabetes.

Every day for Shelton is like living on a seesaw. Lack of insulin causes sugar to stagnate in the blood, causing ketoacidosis and possibly death. But injecting too much insulin does not work, it will cause hypoglycemia.

Shelton once crashed his motorbike into a wall and fainted in a resident's yard while delivering their mail. After that accident, the doctor advised Shelton to retire. His ex-wife Cindy had to take Shelton home to take care of him.

"I was afraid to leave him alone all day," she said.

The first patient cured of type I diabetes

The opportunity with Shelton came in early 2021, when Cindy read an information about a clinical trial by Vertex Pharmaceuticals. The Boston-based biopharmaceutical company is recruiting volunteers who are patients with type I diabetes.

They will be testing a stem cell method that has been developed over decades by a scientist sworn to find a cure for the horrible disease that plagues both of his young children.

Cindy and Shelton signed up to participate. The trial officially began on June 29, and Shelton was selected as the first patient to undergo a therapy called VX-880. In the combined phase I and II clinical trial, he received a half-dose infusion of differentiated islet cells from stem cells via the hepatic portal vein.

From there, the cells would pass through Shelton's pancreas, reside there and replace the cells in his body that had failed. Together with immunosuppressive drugs that allow these cells to survive, they act like a new insulin factory in the body, allowing Shelton to manage his blood sugar.

On the 90th day after the test, tests showed that his HbA1c had dropped from 8.6 to 7.2. Fasting C-peptide, an indicator of endogenous insulin production, increased from 0 to 280 pmol/L. The stimulating C-peptide peaked at 560 pmol/L indicating that Shelton's body had restored its ability to produce glucose-responsive insulin, a function that had disappeared for more than 40 years.

All the numbers showed that VX-880 was effective, Shelton from having to inject 34 units of insulin / day, to day 90 was only needing 2.9 units. "It's like a miracle," he said.

Brian Shelton, a retired postman in Ohio, USA, recently became the first patient in the world to be cured of type I diabetes.

In some ways, Shelton has been cured of type I diabetes. "This is something we've literally been looking forward to after decades," said Dr. Irl Hirsch, a diabetes expert. at the University of Washington said.

In agreement with him is Peter Buttler, a diabetes expert at the University of California. Buttler compares this VX-880 islet stem cell therapy to the discovery of insulin more than 100 years ago.

It would be a new milestone in the treatment of diabetes and could help millions of patients around the world each year, "give them back the cells they lost", Dr. Buttler said.

A journey spanning more than 30 years

The VX-880 is the result of more than 30 years of searching for a diabetes treatment by Doug Melton, a biologist at Harvard University.

Dr. Melton had never known diabetes until 1991, when his 6-month-old son - Sam - became seriously ill. Very strange symptoms include vomiting, shaking and gasping for breath. "Pediatricians [when they looked at the clinical condition] couldn't figure out what it was," Dr. Melton recalls.

It wasn't until he and his wife, Gail O'Keefe, took their child to Boston Children's Hospital that urine tests revealed that the baby had diabetes. Unlike type II diabetes, type I diabetes can be a congenital disease that is inherited and develops very early.

That means Emma, ​​Sam's older sister and Melton's eldest daughter, could also develop the disease within 10 years. At the age of 13-14, the girl will probably officially receive a diabetes diagnosis.

"You've got to find a cure for this damn disease," Gail told Shelton in tears as their little one had to prick his fingertips four times a day. And when the 6-month-old boy's fingers were bruised from the stings, they had to change the position of the needle down to his toes.

The blood sugar of a patient with type I diabetes is a vital indicator, especially for a 6-month-old child. "It's a terrible disease," says Dr. Butler.

Doug Melton, who started out as a biologist at Harvard University, was determined to find a cure for diabetes when his son suffered from the disease at the age of 6 months.

Patients with type I diabetes can have their legs amputated and even die overnight if their blood sugar drops during sleep. For an infant like Sam, a dose of insulin for him was not available. Dr. Shelton and Gail had to calculate to dilute the injections from the adult dose.

This increases the risk of sudden low blood sugar. Not to mention, the disease can weaken the immune system over time. Sam was born with an underlying condition that should only begin at the end of life in older patients.

The boy is at risk of blindness, kidney failure and a host of other secondary diseases if his pancreatic islet cells are not replaced. Until the advent of VX-880, the only therapy to do that was to transplant pancreatic islets from a donor to a patient.

However, the shortage of donated organs makes this approach impossible for the vast majority of patients.

Purple beanie

At the time his son received the diagnosis, Dr. Shelton was working as a biologist at Harvard University. He decided to put aside his research on the development of frogs in search of a cure for diabetes.

Not starting from scratch, frog embryos had previously taught Shelton that human embryonic stem cells could help solve the problem. If islet cell transplantation is not possible for the majority of patients because of the lack of an organ, coaxing the embryonic stem cells to turn into islet cells may be the answer.

Pancreatic islet cells are what produce insulin, but in the body of type I diabetics, they have been destroyed by their own immune systems.

Stem cells are cells that can turn into any cell in the body. The point is to find a formula to guide them, be it biochemical compounds, physical stimuli or anything else.

For each stage of development of the pancreatic islet cell stem cell, it is marked with a colored indicator. Accordingly, stem cells will initially emit red light, it will gradually turn yellow and blue, when signs of pancreatic islet differentiation appear, indicating that the cells have produced insulin.

Finally, if the cells continue to turn purple, it will be a sign that the original stem cells have fully differentiated into islet cells, with full insulin production.

It sounds simple, but after countless experiments taking place over the past two decades, Dr. Shelton and his $50 million invested laboratory are still standing still.

Until one night in 2014, when they decided to work overtime in an experiment that didn't seem very optimistic, the red cells turned blue for the first time and became darker and darker.

Stem cells are cells that can turn into any cell in the body.

The whole lab decided to celebrate with a small party. They buy blue beanie hats and put it on their heads. But for a while after that, the cells were still stuck in blue and couldn't turn purple.

Dr. Melton and his lab really crave purple cells and woolen hats. And they know they need more resources.

A billion dollars in your pocket

Semma biotechnology company was founded in 2014, the name is a combination of Sam and Emma, ​​two children of Dr. Melton. They went on to take five years to develop a stem cell therapy for diabetes.

The 2019 milestone marks the first time that Semma, led by cell therapy expert Bastiano Sanna, has conducted a successful trial of the treatment of diabetes in mice.

The next step they aim to take is a human clinical trial. But Semma was still too young then. They needed a large company, with hundreds of experienced employees, and good capital to lead this experiment.

It has to be done according to the exacting standards of the Food and Drug Administration (FDA) - with thousands of pages of documents that must be prepared and planned in advance.

The opportunity came in April 2019, at a meeting at Massachusetts General Hospital, Dr. Melton came across a former colleague. That's Dr. David Altshuler, who was a professor of genetics and medicine at Harvard but recently took up the position of chief scientific officer at Vertex Pharmaceuticals.

During lunch, Dr. Altshuler asked Dr. Melton if there was anything new in his work. Dr. Melton had taken from his pocket a small glass vial containing a small sparkling purple tablet. "These are the islet cells that we created in Semma," he told Dr. Altshuler.

Given his vision at Vertex as the company is also focusing on biotherapeutics as an alternative to a chemotherapeutic platform, Dr. Altshuler told Melton: "I think there might be an opportunity."

Dr. Melton holds in his hand a glass vial containing stem cells that differentiate into islet cells.

Eight weeks later a series of meetings were held between Vertex and Semma. The company then decided to buy Semma for $950 million. Under the auspices of Vertex, the clinical trial of the VX-880 diabetes stem cell therapy has been approved by the FDA.

They officially launched it in June of this year and Shelton became the first patient selected.

Happy tears

Like pancreatic transplant patients, Shelton, after receiving half a dose of VX-880 stem cells, will still have to take drugs that suppress the immune system, because the cells he received came from a stranger.

However, Shelton says taking the pill causes few side effects. He is much more satisfied with that than having to monitor his blood sugar every day and always fear the dangerous complications of the disease.

Dr. James Markmann, the doctor who performed Shelton's stem cell injection, said that although VX-880 was only a half-dose trial of Vertex, no one would have thought it would work so well. so.

"The results are impressive," says Dr. Markmann, "It's a real step forward in the field."

With the acquisition of Semma for $950 million, Vertex Pharmaceuticals now owns a breakthrough stem cell therapy that promises to help millions of patients around the world cure type I diabetes.

Despite being an early developer of the VX-880, Vertex's regulations after they bought Semma made Dr. Melton one of the last to know the results of the trial.

It wasn't until last month that Vertex was ready to reveal Shelton's condition to him. At the meeting that day, Dr. Melton confessed he wasn't expecting much. "I have prepared a speech that is comforting and encouraging," he said.

But the moment Vertex said their experiment had been successful, Dr. Melton almost burst into tears. Normally a rather quiet and calm person, Dr. Melton became restless during the meeting.

He has devoted decades and all his faith to this project. It was not until the end of the Vertex group's presentation that a bright smile appeared on Dr. Melton's face. All data is real.

That day the doctor left Vertex to go home to dinner with Sam, Emma, ​​and O'Keefe. When the family was seated at the table, he informed them of the results. "I can only say it was a moment of tears and hugs," Dr Melton said.

"The only thing I can say is 'Thank you'" - Brian Shelton.

As for Shelton, the moment of truth came just days after he was injected with VX-880 stem cells. That's when he was discharged home and measured his blood sugar by himself, using the same handheld device that had followed him for decades.

The indicator shows up perfectly! Shelton and his wife Cindy celebrated. And even after their meal ended, Shelton's blood sugar remained within the normal range. He literally cried when he saw the results: "The only thing I can say is 'Thank you'".