ACCELERATING A CURE FOR DIABETES
FROM LABORATORY TO CLINIC
Our goal is to change the course of diabetes.”
— Doug Melton, PhD
Managing a chronic disease like diabetes can be exhausting.
Patients with diabetes must alter their diet and exercise regularly; prick their fingers multiple times a day to test their blood sugar level; and, when that level is high, inject themselves with insulin. Without this constant management, diabetes can lead to serious or even fatal medical complications.
At the Harvard Stem Cell Institute (HSCI), Doug Melton, PhD is changing this paradigm. He is developing a stem cell-based treatment that could allow patients with diabetes to go about their lives as if they did not have the disease—as if they were, effectively, cured.
Melton announced in 2014 that his laboratory was able to produce fully functional human beta cells, the cells in the pancreas that produce insulin, by directing the development of embryonic stem cells. Since that milestone, Melton has leveraged HSCI’s network of hospital and industry collaborators to accelerate the transfer of this technology from the laboratory to the clinic.
BETA CELL TRANSPLANTS
In healthy individuals, beta cells respond to rising blood sugar levels by releasing a precise amount of insulin, which triggers body cells to take up sugars from the bloodstream to use for energy. In patients with type 1 diabetes, an autoimmune response destroys beta cells before they can produce insulin. In patients with type 2 diabetes, beta cells do not produce enough insulin. Furthermore, their bodies may
not respond properly to insulin.
Current treatments require patients to inject themselves with manufactured insulin—Melton’s goal is for patients to produce their own insulin again, through a beta cell transplant.
It took Melton’s team more than a decade to understand how the body makes pancreatic beta cells. They researched hundreds of signals, molecules, and environmental conditions to determine the combination that would cause a stem cell to become a pancreatic precursor cell, then a pancreatic cell, and finally a beta cell.
One challenge the group overcame was to make cells that both looked like beta cells and worked like them, increasing the amount of insulin released in response to rising blood sugar. Melton’s beta cells were the first laboratory-created pancreatic cells to be fully functional when transplanted into animal models. “Making the cells functional was the key advance,” Melton says.
MOBILIZING THE HSCI NETWORK
Reaching out to collaborators who were already connected through the HSCI network, Melton has rapidly mobilized clinical and industry resources as part of the Boston Autologous Islet Replacement Therapy (BAIRT) program.
In 2017, the BAIRT program made substantial progress toward securing approval from the Food and Drug Administration for a clinical trial that tests a new approach: giving patients a supply of their own insulin-producing beta cells.
With their clinical expertise in diabetes and transplants, BAIRT collaborators at Brigham and Women’s Hospital and Joslin Diabetes Center are working directly with patients. For this initial trial, they are working with patients who develop diabetes following surgical removal of the pancreas.
Starting with patient blood samples, the research team will first derive induced pluripotent stem cells, and then use them to generate hundreds of millions of beta cells. HSCI researchers will contribute their knowledge of stem cell biology and derivation techniques. The cells will be produced at the Dana-Farber Cancer Institute’s clinical-grade cell manufacturing facility.
The research team is currently investigating the best site in the body to transplant the beta cells, and how to adapt this therapeutic approach for patients with type 1 or type 2 diabetes.
Semma Therapeutics, a biotechnology company co-founded by Melton in 2015, is also a collaborator in the BAIRT program. Semma is bringing together industry experts to drive preclinical and regulatory strategies for this emerging treatment. In 2017, the company announced that it had raised $114 million in a series B round of funding.
MOVING FORWARD TOGETHER
Because HSCI collaborators span the university, hospital, and biotechnology industry settings, the BAIRT program has been able to assemble the necessary resources quickly to advance this therapeutic approach.
“Our goal is to change the course of diabetes,” Melton says. “It takes a whole community to do this, and I’m excited to see everyone come together to push forward.”