Helmsley Charitable Trust Awards $2.7 Million for Efforts to Prevent Hypoglycemia in Type 1 Diabetes by Restoring Alpha Cell Function

Collaborative Working Group Will Address Barriers to Drug Development in Historically Underfunded Area of Type 1 Diabetes Research

New York, NY—The Leona M. and Harry B. Helmsley Charitable Trust today announced 13 new grants that will fund pilot research projects to identify ways to restore alpha cell function in individuals with type 1 diabetes (T1D). The set of grants will also unite the lead investigators of these projects in a working group, where they will share knowledge in an effort to make therapeutic discoveries. If successful, these pilot projects may lead to long-term efforts to develop new therapies that reduce or prevent hypoglycemia in T1D.

Blood glucose levels are regulated by the pancreas’ beta cells, which secrete insulin that signals to the body to reduce blood glucose levels; and by alpha cells, which secrete glucagon that signals to the body to increase blood glucose levels. T1D eliminates beta cells from the pancreas, resulting in high glucose levels that can only be managed with insulin therapy. Adding to the complexity of this disease, people with T1D also have dysfunctional alpha cells that, during activities such as exercise, permit uncorrected and dangerously low glucose levels that can lead to unconsciousness or even death.

The constant risk of hypoglycemia means that people with T1D must monitor and treat low blood glucose levels with fast-acting carbohydrates or, in the case of emergency, injecting exogenous glucagon. A therapy that could reestablish alpha cells’ ability to detect low glucose levels and secrete glucagon would be a game-changer for glucose management, by reducing or even preventing hypoglycemic episodes.

“Despite clear potential benefits for individuals with T1D, research into human alpha cell dysfunction within the context of T1D has been underappreciated and underfunded,” said Dr. Ben Williams, Program Officer of Helmsley’s Type 1 Diabetes Program. “At Helmsley, we look to invest in promising approaches that could change the lives of people with T1D. We also aim to foster collaboration, and we are excited for the bold ideas of this working group to inform one another so we can together make significant scientific breakthroughs.”

Helmsley’s investment of over $2.7 million supports the following preclinical, clinical, or human sample-based research projects, with the first beginning in November 2017:

  • Joslin Diabetes Center, “Understand cell stress pathways in modulating glucagon release,” led by Dr. Rohit Kulkarni
  • Oregon Health and Science University, “Determine the role of alpha cell heterogeneity in T1D,” led by Dr. Markus Grompe
  • University of California, San Francisco, “Modeling human alpha cell function and dysfunction associated with T1D,” led by Dr. Matthias Hebrok
  • University of Miami, “Pilot studies to understand alpha cell dysfunction and correct glucagon secretion in type 1 diabetes,” led by Dr. Alejandro Caicedo
  • St. Louis University School of Medicine, “A novel target to restore glucagon secretion in individuals with T1D,” led by Dr. Gina Yosten
  • Vanderbilt University, “Improving isolation of pancreatic islets in T1D to assess alpha cell function and gene expression,” led by Drs. Al Powers and David Harlan (University of Massachusetts Medical School)
  • Vanderbilt University, “Normalizing hypoglycemia-induced glucagon secretion in T1D by enhancing calcium handling,” led by Dr. David Jacobson
  • Washington University, “Silence alpha cells as a therapy for T1D,” led by Dr. David Piston
  • Herlev Gentofte Hospital, “Preventing hypoglycemia in type 1 diabetes with the hormone GIP,” led by Dr. Filip Knop
  • Oxford University, “Optimizing glucagon secretion to prevent hypoglycemia in T1D,” led by Dr. Patrik Rorsman
  • University of Dundee, “Understanding the hypoglycemia-specific defect in alpha-cell glucagon secretion using a humanized mouse model of T1D,” led by Dr. Rory McCrimmon
  • Université catholique de Louvain, “Study of the mechanisms of control of glucagon secretion in human islets and the long-term effect of low/high glucose,” led by Dr. Patrick Gilon
  • Uppsala University, “Islet cell signaling regulating glucagon secretion,” led by Dr. Anders Tengholm

“Insulin therapy is life-saving and remains the core treatment for individuals with T1D. However, because it can increase the risk of hypoglycemia, novel approaches for curtailing the risk of low blood sugar are highly warranted,” said Dr. Filip Knop, Director of the Center for Diabetes Research at Gentofte Hospital. “We are hopeful that this research may shed light on promising approaches to restore alpha cell function and prevent hypoglycemia.”

“We still do not fully know why individuals with T1D are particularly susceptible to hypoglycemia, partly because our understanding of alpha cell function is quite limited,” said Dr. Alvin C. Powers, Chief of the Division of Diabetes, Endocrinology, and Metabolism at the Vanderbilt University School of Medicine. “Because of new technologies for studying the alpha cell, promising opportunities like this effort to understand T1D’s underlying alpha cell dysfunction are the first step to developing therapies to correct it.”

“Maintaining optimal glycemic control is incredibly difficult and burdensome for individuals with T1D,” said Dr. Gina Agiostratidou, Program Director of Helmsley’s Type 1 Diabetes Program. “With these grants, we hope to advance our understanding of T1D and discover potential solutions that drive our larger goal of helping the millions of people living with T1D better manage this complex disease.”

###

About the Helmsley Charitable Trust

The Leona M. and Harry B. Helmsley Charitable Trust aspires to improve lives by supporting exceptional efforts in the U.S. and around the world in health and select place-based initiatives. Since beginning active grantmaking in 2008, Helmsley has committed more than $2 billion for a wide range of charitable purposes. For more information, visit www.helmsleytrust.org

Contact

Laura Fahey, lfahey@helmsleytrust.org, 212-953-2814