Delaying Diabetes in At-Risk Young People

For more than 30 years, UCSF immunologist Jeffrey Bluestone, PhD, has believed that a drug he and his team developed in 1986 could stop the onset of type 1 diabetes – if given the right chance. 

His research showed that the drug would act like a “magic bullet” to target the body’s out-of-control T cells before they destroyed insulin-producing beta cells in the pancreas and triggered the autoimmune disease that afflicts almost 2 million people in the US. 

But he had to wait for both the right drug strategy and for the pharmaceutical industry to catch up with the science. “It’s not just something we threw at the wall and hoped would stick,” said Bluestone, director of the Hormone Research Institute in the Diabetes Center at UCSF. “The science told us this should work, so we kept at it.” 

In June 2017, Bluestone’s research was validated when the American Diabetes Association announced the successful outcome of an eight-year drug trial conducted by Bluestone’s collaborator, Kevan Herold, MD, of Yale University, in partnership with national institutions including UCSF. Turns out the key to the drug’s success was to dose people at high risk for diabetes before their bodies succumbed the disease. 

Bluestone called the difference between the group treated with the drug – now called teplizumab – and the group dosed with a placebo “profound.” The trial found that a two-week course of the drug delayed type 1 diabetes in patients by two years, and may have permanently delayed disease onset in some young patients. Postponing diabetes by even a short time can reduce chronic health challenges such as loss of limbs, blindness, and heart disease that patients face throughout their lives. 

Bluestone isn’t surprised by the drug’s success, nor the fact that it took so long. The pharmaceutical industry used to regard antibodies – which are proteins in our bodies that fight disease – as too difficult to make, too risky, and too expensive to develop as medicine. 

“It is hard to believe this now – when half of the drugs that come to market these days are antibodies – but at the time, many pharmaceutical companies didn’t believe they would make it as drugs,” he says. 

But the scientist remained confident that this drug developed so long ago in his lab at the University of Chicago would prove to be a potent therapeutic by engaging the body’s own immune system. Finally, he was proven right. 

“We’ve always stayed very focused on understanding how and why this drug should work at a biological level,” Bluestone says. “In the end, that’s why I’ve been at this for more than 30 years.” 

Dr. Jeffrey Bluestone is the A.W. and Mary Margaret Clausen Distinguished Professor of Endocrinology and Metabolism and president and CEO of the Parker Institute for Cancer Immunotherapy.