Could a 100-year-old vaccine treat Type 1 diabetes? MGH researchers are working to find out. – The Boston Globe

Studies have tied the vaccine to lower rates of childhood mortality and stronger immunity against a host of infectious diseases. There are also signs the vaccine can calm the immune system, benefiting people with allergies and autoimmune diseases.

Around the world, trials are underway to research BCG in multiple sclerosis, Alzheimers, and COVID-19.

Faustmans lab, in partnership with NYU Langone Health, is recruiting 150 adolescents with Type 1 diabetes for pediatric clinical trials of the shots. All participants must be between the ages of 12 and 17 and have had the disease for at least two years.

The research builds on studies Faustman has conducted over the last decade.

A small phase 1 clinical trial, published in 2012, showed BCG prompted higher levels of insulin production than in placebo-treated subjects. In a long-term follow of the trial, published in 2018, Faustmans lab found that adult patients with diabetes treated with the vaccine experienced 10 to 18 percent reductions in blood sugar levels and were able to use less insulin. Diabetic patients in the same trial who were treated with a placebo showed almost no improvement.

Research has found that reducing levels of hemoglobin A1c, a measure of blood glucose, by even 10 percent can lower the risk of lifelong complications from diabetes.

A phase two clinical trial, begun in 2015 with 150 patients, is ongoing, with results expected in a year and a half.

Faustman said BCG appears to help patients with Type 1 diabetes by altering their immune system.

In individuals with the disease, the body produces abnormal white blood cells that attack insulin-secreting cells in the pancreas.

Faustmans research suggests BCG can turn on good white blood cells and destroy bad white blood cells prone to attacking the pancreas. Further, the vaccine fixes defects in the white blood cells of diabetes patients, allowing the cells to process sugar and draw more of it out of the blood, Faustman said.

Key to BCGs potency, Faustman and others believe, is the fact that it is a live vaccine. It uses a weakened form of the bacteria that cause tuberculosis, reintroducing a key microbe to the body that humans stopped interacting with as society became more hygienic.

Its amazing to think about how a bug could, over a period after vaccination, reprogram cells in permanent ways that result in immune responses, Faustman said.

Faustmans research, which is still in early stages, has met with controversy.

After she published her phase 1 research in 2018, JDRF, formerly known as the Juvenile Diabetes Research Foundation, and the American Diabetes Association issued a joint statement saying it wasnt clear that lowered insulin levels were a direct result of the vaccine, as levels tend to change over time, and said the small number of participants wasnt robust enough to be generalized to the larger population.

In a statement to the Globe, JDRF said its position on Faustmans research had not changed.

The ADA did not respond to a request for comment.

Other researchers also have been skeptical.

Its not something being pursued or taken seriously by the rest of the field, said Stephan Kissler, a Type 1 diabetes researcher at Joslin Diabetes Center.

Other more mainstream diabetes experts are pursuing avenues such as immunosuppression and creating insulin-producing cells out of stem cells that can be transplanted back into patients bodies. Kissler works to genetically alter transplanted cells so they dont require recipients to take immunosuppressants.

We want to change their disease, said Kissler.

Yet Faustman sees her work as a stepping stone to do just that. The pediatric clinical trial will focus on children who are at an early enough stage in the disease to still have some pancreas function.

When we go into older people, they have no pancreas reserve, Faustman said. So were only testing in them what does BCG do to become a better regulator of glucose metabolism. Now, when we go into kids, it tests the ability of BCG to possibly preserve the pancreas as well as change these sugar defects.

Its an exciting population to study. You get to see if you stop the immune response, can the pancreas recover or become more stable as well as getting white blood cells to behave.

Dr. Joseph Bellanti, a professor emeritus of pediatrics and microbiology-immunology at Georgetown University Medical Center, said the work is innovative and the clinical trials conducted so far were encouraging.

People are entitled to their opinions. My opinion is they are on to something. And its worthy of being pursued, he said.

Ultimately, Faustman hopes to begin another set of clinical trials by the end of this year in children who have just been diagnosed with diabetes, which could change the course of the disease even earlier.

She is undeterred by the skepticism, saying the number and scope of clinical trials involving BCG speaks to its promise.

When you see a global momentum to study these off-target effects in humans, you start to see the validity of reintroducing this microbe, Faustman said.

Jessica Bartlett can be reached at jessica.bartlett@globe.com. Follow her on Twitter @ByJessBartlett.

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Could a 100-year-old vaccine treat Type 1 diabetes? MGH researchers are working to find out. - The Boston Globe