“I remember watching it as a child,” said Kelly Bennett, reminiscing about the annual Tournament of Roses Parade every New Year’s Day in Pasadena, California. Growing up in Missouri, Kansas, Virginia, Oklahoma and Arizona, Bennett’s parade thrills came remotely, watching on TV along with millions of others.
But this coming Jan. 1, Bennett, a 52-year-old psychotherapist, social worker and single mom with two kids in college, will get her once-in-a-lifetime opportunity to experience the big spectacle in person. She’ll be riding aboard City of Hope’s parade float (named “A Beautiful Day for Hope”) alongside the physician who changed her life, Fouad R. Kandeel, M.D., Ph.D., also participating for the first time.
“It’s an honor and I’m very excited,” Bennett said. “It’s going to be surreal. I want to savor the experience.”
Dr. Kandeel, the Arthur D. Riggs Distinguished Chair in Diabetes & Metabolism Research, has enabled Bennett, a type 1 diabetic since age 6, to live without daily insulin injections.
Bennett took part in a clinical trial involving islet cell transplantation aided by synthetic gastrin, a revolutionary process that seeks to replace critical insulin-producing cells destroyed by type 1 diabetes. “Kelly did fantastically well,” said Dr. Kandeel, adding that, while not a cure, the transplanted cells could very well keep working for decades, if not longer. “My first patient, back in 2004, is still insulin free,” he said.
Bennett remembers how, as a first-grader in Wichita, Kansas, she became ill with what appeared to be the flu. “My parents had no clue,” she recalled. A short time later, “I woke up and couldn’t find the bathroom. I couldn’t comprehend anything.” This alarmed her parents enough to rush little Kelly to the hospital, where doctors recognized the signs of type 1 diabetes.
“The brain eats glucose,” explained Dr. Kandeel. “Bad things happen” when the brain’s sugar supply is diminished. “People can become confused, even belligerent.” Low sugar, or hypoglycemia, can also accelerate the heartbeat, cause sweating and dizziness and even lead to seizures.
Some people — and Bennett believes this was happening to her — experience hypoglycemia without realizing it, especially during the night, waking with a serious imbalance and unable to function normally, like finding the bathroom. Bennett’s mother would wake her up in the middle of the night to check her blood sugar. In college, Bennett remembers sleeping through her alarm clock going off each morning, too tired to get up.
Ultimately, Bennett learned how to handle her type 1 diabetes. When wearable blood sugar monitoring devices came out, she was among the first to get one. “I always had exceptional diabetes care,” she said. And no complaints.
Except one.
She hated the daily dependence on insulin. She dove into research and asked around for something, anything, that could help. A Facebook group pointed her to several clinical trials, but most would not accept her. Until she found City of Hope®, a place she knew nothing about.
Joining an Islet Cell Transplantation Trial
Islet cell transplantation involves taking insulin-producing cells from a donor pancreas and implanting them into a patient’s liver, considered a better site than the patient’s own autoimmune-compromised pancreas. If the cells engraft successfully and begin secreting insulin in their new host, the patient’s need for insulin should decrease or even disappear.
Early attempts, beginning in 1980, had mixed results. Things improved after 2000 when a team at the University of Alberta, Edmonton, devised an improved protocol that called for specific immunosuppressive drugs, along with doing an average of two sequential transplants to achieve the desired result.
Dr. Kandeel’s research aimed to eliminate a patient’s need for insulin in just one transplant procedure. It would not be easy. “First of all, you need 10,000 islets per kilo of body weight. That can require two or three procedures,” he said. “Also, inflammation can kill half the implanted cells.”
So how to multiply the number of islet cells while preventing inflammation? Dr. Kandeel believed the answer was gastrin.
As a fetus develops, a supply of the hormone gastrin resides in the pancreas, helping to produce those critical islet cells. At birth, gastrin leaves the pancreas and migrates to the stomach, where it regulates acid secretion.
Adding gastrin to the transplant process increases islet production, reduces inflammation and protects the transplanted cells so more of them survive. To ensure a stable supply of the hormone, “we decided to make it in the lab,” Dr. Kandeel said.
Bennett was thrilled to join the ongoing trial — begun in 2019 — and delighted to meet Dr. Kandeel, a 30-plus year veteran of City of Hope. “He was great,” she recalled. “Such a jovial guy, always happy, always excited, dedicated to helping people who struggle. He’s a kind, wonderful man.”
To prepare for the transplant, Bennett received twice-daily injections of gastrin for a month. Then, on Sept. 11, 2023, she underwent the 20-minute procedure under conscious sedation. Results came rapidly. Within a week, she no longer needed insulin. More than a year later, she still doesn’t. She needs to carefully monitor her diet, and she continues to take three immunosuppressant drugs, as well as medications to protect the liver and stabilize her blood pressure. But those daily insulin injections are a thing of the past.
Others in the trial have experienced similar success. A report in Diabetes magazine (published by the American Diabetes Association) said that “Gastrin use in the peri-transplant period leads to rapid engraftment, larger magnitude of insulin reduction and permitted achievement of insulin independence in more than half of subjects after a single islet transplant of less than half the normally targeted islet dose.” Success all around.
Nevertheless, Kandeel sees room for improvement and he’s working on a variety of paths, including finding less toxic locations than the liver for implantation. Two possibilities: the abdominal wall and the omentum — the membrane surrounding the stomach and other abdominal organs.
Other ideas being considered include gene-editing to prevent rejection of the transplanted cells and diminish the need for immunosuppression. It may also be possible to create islet cells from stem cells, something already attempted successfully in animal studies. Better imaging systems are being developed to give a clearer view of islet cells. And researchers are working on a longer-acting version of gastrin, so it can be administered once a week instead of twice a day.
For now, Dr. Kandeel is looking forward to seeing Bennett aboard the City of Hope float. “I want to congratulate her on her achievement,” he said, praising her motivation and diligence. “She’s done an excellent job.”
He expects he’ll see other patients there as well, which should make for several happy reunions. “The fact that they do so well, they become a mark in your life. We take care of them for so long, we treat them like family.”
Bennett, who says she feels “truly blessed,” will have a message for Dr. Kandeel, too.
“I’m going to give him a great big hug!”