Researchers at the Mount Sinai Diabetes Center have already developed an artificial pancreas. Next, a drug that could regenerate pancreatic cells in the body.
Sixty years ago, two New Yorkers, Rosalyn Yalow and Solomon Berson, developed radioimmunoassay, a technique that permitted measurement of insulin levels in blood. That discovery allowed them to prove, for the first time, that type 1 diabetes is characterized by insulin deficiency while type 2 diabetes results from insulin resistance. Their work earned Berson and Yalow faculty positions at the Mount Sinai School of Medicine in 1968, and led to a Nobel Prize in 1977.
Today, the Icahn School of Medicine at Mount Sinai remains at the forefront of diabetes research. “Here at the Mount Sinai Diabetes Center, we have an extensive research program for both type 1 and type 2 diabetes, with investigators performing basic and translational research in addition to clinical trials,” says Carol Levy, the center’s director. “We typically have 8 to 12 active clinical diabetes research studies going on at any time.”
Diabetes is now considered a global epidemic. “420 million people around the world have diabetes—30 million of them in the United States,” says Andrew Stewart, professor and director of Mount Sinai’s Diabetes, Obesity and Metabolism Institute.
For those living with diabetes, managing the disease can be onerous. It can require lifestyle modifications, insulin therapy, oral medication, and the monitoring of blood sugar levels many times each day. Levy and Stewart oversee research that could significantly reduce that burden.
Levy has spent the past four years developing and improving systems that could serve as an artificial pancreas. “These devices pair glucose sensors with an algorithm that sends directions to an insulin pump for insulin delivery, to anticipate changes to blood sugar levels,” Levy says. “Based on those predictions, the controller [either housed in the insulin pump or on a smart phone] instructs the insulin pump to release more or less insulin to mitigate any blood sugar spikes or drops before they become significant.” By automating the insulin delivery, these systems stabilize blood sugar levels and reduce the burden of care.
“I was initially leery of the concept, but at Mount Sinai, patients have experienced tremendous results,” Levy says. “Patients are so enthusiastic about these devices, which continue to become more sophisticated, that most don’t want to give them back at the end of studies.”
Stewart and his team are following a different line of research: they are focused on developing drugs that are able to regenerate the insulin-producing beta cells in the pancreas that are missing in people with diabetes. “My lab is working on drugs to expand a patient’s remaining beta cells, whether that patient has type 1 or 2 diabetes,” Stewart says. “In 2015, we did a robotic high-throughput screen of 100,000 drug-like molecules and identified harmine, the first drug that induces human beta-cell regeneration, a finding that has now been reproduced by 20 to 30 labs around the world.”
In 2018, in a collaboration with the Genomics, Bioinformatics, and Drug Discovery programs at Mount Sinai, the Stewart group reported the use of next-generation DNA and RNA sequencing to identify pathways to discovery of additional beta cell regenerative drugs. “For this study, we collected a large series of insulinomas—benign tumors of pancreatic beta cells that also overproduce insulin,” Stewart says. “We sequenced 38 of these tumors, which gave us a ‘genomic recipe’ or ‘roadmap’ for what it takes to make beta cells grow and continue to make insulin.” Using that map as a guide, Stewart has now identified additional drugs that will be more easily tolerated than harmine (which can have effects on organs other than the pancreas) and can regenerate beta cells at a higher rate. “We’re in the process of publishing follow-up articles, and we have filed for several related patents,” Stewart reports.
Both research areas are developing rapidly. “The first-generation artificial pancreas was rolled out in the spring and summer of 2017,” Levy says. “At the moment, we’re working on a second generation, to meet the needs of many more patients, which could be available in 2019. Now what we need is for patients to have more device options, and for the insurance companies to broaden coverage.”
Beta-cell regeneration is also moving quickly. “Two years ago, there were no drugs to make beta cells regenerate,” Stewart says. “Now we have several. They’re not yet ready for use in the clinical population, but that should change within 5-10 years.”