Is There a Treatment for Type 1 Diabetes? It Appears to Have Worked For One Man.

Type 1 diabetes governed Brian Shelton's life.

He would fall consciousness without warning when his blood sugar dropped too low. He collided with a wall on his motorcycle. While delivering mail, he passed out in a customer's yard. After that incident, his supervisor advised him to leave the Postal Service after a quarter-century of service. He was 57 years old at the time.

Cindy Shelton, his ex-wife, welcomed him into her home in Elyria, Ohio. “I was afraid to leave him alone all day,” she said.

She saw an advertisement for patients with Type 1 diabetes to enroll in a research study by Vertex Pharmaceuticals earlier this year. The company was put to the test a medication developed by a scientist who pledged to discover a cure after his baby boy and then his teenage daughter was diagnosed with the fatal condition.

The first patient was Mr. Shelton. On June 29, he received an injection of stem cell-derived cells that functioned similarly to the insulin-producing pancreas cells his body lacked.

His body now regulates his insulin and blood sugar levels on its own.

Mr. Shelton, now 64, could be the first person to be cured of Type 1 diabetes thanks to a new medication that has scientists hopeful that relief is on the way for many of the 1.5 million Americans who suffer from the disease.

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

Experts in the field of diabetes were taken aback, although care was advised. The trial, which will last five years and involve 17 persons with severe Type 1 diabetes, is still ongoing. It is not indicated as a treatment for Type 2 diabetes, which is more frequent.

“We’ve been looking for something like this to happen literally for decades,” said Dr. Irl Hirsch, a University of Washington diabetes expert who was not involved in the study He wants to see the outcome, which has yet to be published in a peer-reviewed publication, reproduced in a large number of people. He also wants to know if there will be any unexpected side effects, as well as whether the cells will last a lifetime or if the treatment would need to be repeated.

But, he said, “bottom line, it is an amazing result.”

Dr. Peter Butler, a U.C.L.A. diabetes expert who was not involved in the study, concurred, but with the same concerns.

“It is a remarkable result,” Dr. 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 began with Doug Melton, a Harvard University biologist, on a 30-year search.

'A Terrible, Terrible Illness'

Dr. Melton had never given diabetes any thought until his 6-month-old baby child, Sam, began trembling, vomiting, and panting in 1991.

“He was so sick, and the pediatrician didn’t know what it was,” Dr. Melton said. His and Gail O'Keefe's baby was taken to Boston Children's Hospital. Sam's pee was sugary, indicating that he had diabetes.

The condition begins at the age of 13 or 14, when the body's immune system destroys the pancreas' insulin-secreting islet cells. Type 1 diabetes, unlike the more frequent and milder Type 2, is rapidly fatal unless patients receive insulin injections. Nobody gets better on their own.

“It’s a terrible, terrible disease,” said Dr. Butler at U.C.L.A.

Diabetes is the main cause of blindness in the United States, therefore patients are at danger of turning blind. It's also the most common reason for renal failure. Because their blood sugar drops during sleep, people with Type 1 diabetes are at risk of having their legs amputated and dying at night. They are far more likely to have a heart attack or stroke if they have diabetes. Covid-19 impairs the immune system; one of Dr. Butler's completely immunized diabetes patients died from it lately.

The expensive expense of insulin, which has climbed year after year, adds to the disease's burden.

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 is the only cure that has ever worked. However, for the vast majority of people with the condition, such a strategy is impossible due to a lack of organs.

“Even if we were in utopia, we would never have enough pancreases,” said Dr. Ali Naji, Mr. Shelton was treated in a trial led by a transplant surgeon at the University of Pennsylvania who pioneered islet cell transplants and is now a principal investigator for the project.

Blue Clues

Caring for a young infant with the condition was terrible for Dr. Melton and Ms. O'Keefe. Ms. O'Keefe had to prick Sam's fingers and feet four times a day to assess his blood sugar. She then had to administer insulin to him. Insulin was not even sold in the right dose for a baby that young. It was necessary for his parents to dilute it.

“Gail said to me, ‘If I’m doing this you have to figure out this damn disease,’” Dr. Melton recalled.

Their four-year-old daughter Emma, who was four years older than Sam at the time, would eventually catch the condition when she was 14.

Dr. Melton had been researching frog development but had given up since he was determined to find a diabetic treatment. He chose embryonic stem cells, which have the ability to transform into any cell in the body. His goal was to convert them into islet cells that may be used to cure patients.

One issue was that the cells were derived from discarded fertilized eggs obtained from a reproductive clinic. However, in August 2001, President George W. Bush made it illegal to use federal funds for research involving human embryos. Dr. Melton had to separate his Harvard stem cell lab from the rest of the university. He was able to secure private money from the Howard Hughes Medical Institute, Harvard, and donors to establish a wholly distinct lab, complete with an accountant who tracked all of the lab's expenses down to the light bulbs.

Dr. Melton thinks the experiment cost $50 million over the 20 years it took the lab of 15 or so workers to effectively convert stem cells to islet cells.

The goal was to discover out what chemical instructions would cause stem cells to transform into insulin-secreting islet cells. The research entailed deciphering normal pancreatic development, determining how islets are formed in the pancreas, and running infinite tests to direct embryonic stem cells to become islets. It was a long process.

After years of failure, a small group of researchers, including Felicia Pagliuca, a postdoctoral researcher, returned to the lab one night in 2014 to conduct yet another experiment.

“We weren’t very optimistic,” she said. They'd dyed the liquid in which the stem cells were developing. If the cells produced insulin, the liquid would turn blue.

Her spouse had already called to inquire about her arrival. Then she noticed a faint blue hue that grew in intensity. She was overjoyed, as were the others. They had created working pancreatic islet cells from embryonic stem cells for the first time.

A little party and cake were held in the lab to commemorate the occasion. Then they had bright blue wool caps fashioned for themselves with five colored circles to depict the stages the stem cells had to go through to become operational islet cells: red, yellow, green, blue, and purple. They'd always wished for purple but had always ended up with green.

Dr. Melton's next step was to form a firm, recognizing that he'd need additional resources to develop a medicine that could be commercialized.

Moments of Truth

Semma, a combination of Sam and Emma's names, was formed in 2014.

One of the challenges was figuring out how to generate islet cells in big quantities using a manner that could be replicated by others. It took five years to accomplish this.

The company, directed by cell and gene therapy expert Bastiano Sanna, tested its cells in mice and rats, demonstrating that they worked effectively and cured diabetes in rodents.

The following phase, a clinical trial in patients, required a large, well-funded, and experienced organization with hundreds of people at that point. Everything had to be done to the FDA's stringent criteria, which meant preparing thousands of pages of documentation and planning clinical studies.

Chance came to the rescue. Dr. Melton ran into a former colleague, Dr. David Altshuler, who was a professor of genetics and medicine at Harvard and the deputy director of the Broad Institute, during a meeting at Massachusetts General Hospital in April 2019. Dr. Altshuler, who had recently been promoted to Vertex Pharmaceuticals' chief scientific officer, asked Dr. Melton what was new over lunch.

Dr. Melton removed a little glass vial containing a brilliant purple pellet.

“These are islet cells that we made at Semma,” he told Dr. Altshuler.

Vertex focuses on human diseases with well-understood biology. Dr. Altshuler informed him, "I think there might be an opportunity."

Meetings ensued, and Vertex purchased Semma for $950 million eight weeks later. Dr. Sanna was promoted to executive vice president at Vertex as a result of the purchase.

The company will not reveal the cost of its diabetes medication until it has received FDA approval. However, it is likely to be costly. Vertex, like other businesses, has infuriated patients by charging exorbitant rates for treatments that are difficult and expensive to manufacture.

The problem for Vertex was to ensure that the manufacturing method worked every time and that the cells were safe to inject into patients. Employees operating in sterile environments kept an eye on capillaries containing nutrition and biochemical signals as stem cells transformed into islet cells.

The FDA approved Vertex to commence a clinical trial with Mr. Shelton as the first patient less than two years after Semma was acquired.

Mr. Shelton, like patients who receive pancreas transplants, must take medicines that suppress his immune system. He claims they have no negative effects and are significantly less time-consuming and dangerous than constantly monitoring his blood sugar and using insulin. To keep his body from rejecting the injected cells, he'll have to keep taking them.

However, Dr. John Buse, a diabetes expert at the University of North Carolina who is unaffiliated with Vertex, expressed concern about immunosuppression. “We need to carefully evaluate the trade-off between the burdens of diabetes and the potential complications from immunosuppressive medications.”

According to Dr. James Markmann, Mr. Shelton's surgeon at Mass General who is working with Vertex on the experiment, Mr. Shelton's therapy, known as an early phase safety trial, required careful follow-up and necessitated starting with half the dose that would be used later in the trial. No one expected the cells to work as effectively as they did, he added.

“The result is so striking,” Dr. Markmann said, “It’s a real leap forward for the field.”

Last month, Vertex was ready to reveal the results to Dr. Melton. He did not expect much.

“I was prepared to give them a pep talk,” he said.

Dr. Melton, who is typically a quiet man, became agitated during what felt like a crucial moment. He had poured his heart and soul into this effort for decades. He had a large smile on his face towards the end of the Vertex team's presentation; the data was true.

He left Vertex and returned home to Sam, Emma, and Ms. O'Keefe for supper. Dr. Melton informed them of the results as they sat down to eat.

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

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

Mr. Shelton wept when he saw the measurement.

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

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