Tests under way to see if controlling immune system might curb Type 1 diabetes
Experiment seeks to head off Type 1 diabetes
PITTSBURGH — The doctor had barely pulled away the needle when a blister appeared on Tracey Berg-Fulton’s abdomen: An experimental shot was revving up the 24-year-old’s immune system — part of a bold quest to create a vaccine-like therapy for diabetes.
“If we’re right, that is what’s going to stop Type 1 diabetes,” said Dr. David Finegold as he watched the blisters appear — one to match each of four shots — with intense satisfaction.
It’s a big “if.” The research is in its infancy, a first-step experiment to be sure the vaccine approach is safe before researchers at Children’s Hospital of Pittsburgh test their real target — kids newly diagnosed with this deadliest form of diabetes.
It’s also part of a big shift: Scientists increasingly hope to control Type 1 diabetes by curbing the rogue immune cells that cause it, before patients become completely dependent on daily insulin injections to survive.
“Treating at onset in children is the best chance we have,” said Pittsburgh immunologist Dr. Massimo Trucco, whose novel vaccine — made from patients’ own blood — is among a handful of possible immune therapies being tested around the country.
About 3 million Americans have Type 1 diabetes, where the body mistakenly attacks and destroys cells in the pancreas that produce insulin, the hormone crucial to converting blood sugar to energy. It’s different from the far more common Type 2 diabetes that is usually linked to obesity, where the body produces insulin but gradually loses the ability to use it properly. Type 2 patients have more treatment options, including diet and exercise.
To stay alive, Type 1 patients must rigorously inject insulin, or wear a pump that infuses it.
“It bothers me all the people who say, ‘Can’t you just exercise and get rid of it?’” said Berg-Fulton of Millvale, Pa., who was diagnosed just before her 10th birthday. “Type 2 gets all the attention. This is Type 1 — we die from this.”
Hence the new push for immune therapy. Preserve enough precious insulin-producing cells before irreversible damage is done and maybe patients would need far less insulin, perhaps only occasional injections like when they splurge on ice cream.
But how? A “therapeutic vaccine” must shut down T cells that are the immune system’s attack dogs, racing out to tackle infections or other invaders — but only the faulty ones that erroneously attack a Type 1 diabetic’s own pancreas. Body-wide immune suppression would leave patients vulnerable to other illnesses.
Drug companies are biologically engineering antibodies to disarm those T cells. Two competing teams — MacroGenics Inc. and Eli Lilly, and Tolerx Inc. and GlaxoSmithKline — have advanced tests under way. Also, an experimental drug made from a kind of bone marrow stem cell might tamp down overly aggressive T cells.
Rather than a drug, Trucco’s government-funded strategy: He blocks the 911 call that different white blood cells send to direct T cells to the pancreas. They’re called dendritic cells, and altering three communication molecules on their surface basically confuses and paralyzes the T cells. In mice and monkeys, the reprogrammed cells ended the vicious cycle of a pancreas attack that in turn attracts more T cells to attack again.
Now to try it in people.
“It’s a neat concept,” said Dr. Jay Skyler of the University of Miami, who heads a consortium of diabetes specialists that is closely watching Trucco’s experiment. “It has a whole lot of potential.”
Exploring all the different immune-altering methods is important because combinations may be needed, said Dr. Richard Insel of the Juvenile Diabetes Research Foundation. Maybe a quick hit on T cells like antibodies might offer, followed by some gentler cell-based vaccines to keep them in check. But “these are early days,” he cautioned.
“I’m getting poked for science,” joked Berg-Fulton as Finegold, an endocrinologist and geneticist at Children’s, readied her shots last week.
Back in April, Berg-Fulton donated her own blood so researchers could filter out immature dendritic cells and reprogram them. Reinject them just inside the skin over the pancreas — no deeper than a pinprick — and Trucco’s animal experiments show the cells somehow find their way back to that organ to start working.
That might be too much poking for children; Trucco also is developing a more drug-like way to alter dendritic cells without removing them first.
For now, Berg-Fulton is part of a safety test, one of 15 adult diabetics being injected to make sure there are no unexpected side effects before researchers test if reprogrammed cells might really protect children’s pancreas cells. Even if the vaccine ultimately works, she’s had diabetes too long to benefit, Finegold carefully explained when she volunteered.
“I’d be lying to say I’m not a little disappointed” at that, Berg-Fulton told him. Think long-term, Finegold responded. If doctors one day learn to restore insulin production, they’ll need to keep the faulty immune system from just destroying it again.
EDITOR’S NOTE — Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
On the Net:
Diabetes studies: www.clinicaltrials.gov
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