News & Research: Press Release
PRESS RELEASE: FEBRUARY 22, 2005
Contacts: Becky Ceraul 410-706-7590
Ellen Beth Levitt 410-328-8919
POTENTIAL METHOD FOR PREVENTING TYPE 1 DIABETES
DISCOVERED AT UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE
Contacts: Becky Ceraul 410-706-7590
Ellen Beth Levitt 410-328-8919
POTENTIAL METHOD FOR PREVENTING TYPE 1 DIABETES
DISCOVERED AT UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE
Study Findings Published in Proceedings of National Academy of Sciences
Scientists at the University of Maryland School of Medicine in Baltimore have identified a way to prevent Type I diabetes in rats that are
genetically prone to develop the disease. The discovery could one day lead to the prevention, and possibly to the treatment, of autoimmune
diseases such as Type 1 diabetes, which affects more than one million people in the United States. The findings are published in the February
22, 2005 edition of the Proceedings of the National Academy of Sciences.
In the study led by Alessio Fasano, M.D., professor of pediatrics, medicine and physiology and director of the University of Maryland Mucosal
Biology Research Center, researchers used an animal model of diabetes and found a way to prevent the disease by changing the permeability
of the intestinal wall.
Earlier research by Dr. Fasano and colleagues led to the discovery of the human protein zonulin. They observed that zonulin regulates the
permeability of the intestines by controlling the opening and closing of specialized structures that act like gates between cells. When the body
produces too much zonulin, these gates get stuck open for too long and allow undigested foodstuff, toxins and other bacterial and viral particles
access to the immune system. That contact, in turn, leads to the production of antibodies that can destroy the insulin-producing islet cells in the
pancreas among people genetically predisposed to develop Type 1 diabetes. The final result is the appearance of Type 1, or insulin-
dependent, diabetes.
Dr. Fasano’s group also discovered that zonulin is produced in very large amounts in people who have autoimmune disorders such as
diabetes, celiac disease, multiple sclerosis and rheumatoid arthritis. The researchers performed their latest study on rats that were genetically
prone to develop Type 1 diabetes.
“With autoimmune diseases, the body mistakes its own tissues as foreign, resulting in an attack and destruction by the body’s own immune
system. These diseases are all characterized by an extremely permeable intestinal wall,” says Dr. Fasano. “We already knew that there was a
distinct connection between an increase in zonulin levels and an increased permeability of the intestines. With this study, we’ve been able to
identify a way to prevent zonulin from causing leakage from the intestines as it does in people with these autoimmune diseases.”
With funding from the National Institutes of Health, Dr. Fasano and his research team used diabetes-prone rats to test the effectiveness of a
zonulin inhibitor peptide called AT-1001, which is known to prevent zonulin from regulating intestinal permeability. The peptide prevented the
development of diabetes in the vast majority of the animals tested. Only 27 percent of those that were given water containing AT-1001
developed diabetes. “In essence, we saw that this peptide stopped the sequence of events that leads to diabetes,” Dr. Fasano says.
Dr. Fasano adds that this significant discovery could eventually lead to the development of an oral medication to arrest autoimmune diseases
in the early stages. Immediate plans call for clinical trials to test the use of AT-1001 in patients with celiac disease. Alba Therapeutics, a
Baltimore-based biopharmaceutical company, has already sought approval from the FDA to conduct those trials.
Scientists at the University of Maryland School of Medicine in Baltimore have identified a way to prevent Type I diabetes in rats that are
genetically prone to develop the disease. The discovery could one day lead to the prevention, and possibly to the treatment, of autoimmune
diseases such as Type 1 diabetes, which affects more than one million people in the United States. The findings are published in the February
22, 2005 edition of the Proceedings of the National Academy of Sciences.
In the study led by Alessio Fasano, M.D., professor of pediatrics, medicine and physiology and director of the University of Maryland Mucosal
Biology Research Center, researchers used an animal model of diabetes and found a way to prevent the disease by changing the permeability
of the intestinal wall.
Earlier research by Dr. Fasano and colleagues led to the discovery of the human protein zonulin. They observed that zonulin regulates the
permeability of the intestines by controlling the opening and closing of specialized structures that act like gates between cells. When the body
produces too much zonulin, these gates get stuck open for too long and allow undigested foodstuff, toxins and other bacterial and viral particles
access to the immune system. That contact, in turn, leads to the production of antibodies that can destroy the insulin-producing islet cells in the
pancreas among people genetically predisposed to develop Type 1 diabetes. The final result is the appearance of Type 1, or insulin-
dependent, diabetes.
Dr. Fasano’s group also discovered that zonulin is produced in very large amounts in people who have autoimmune disorders such as
diabetes, celiac disease, multiple sclerosis and rheumatoid arthritis. The researchers performed their latest study on rats that were genetically
prone to develop Type 1 diabetes.
“With autoimmune diseases, the body mistakes its own tissues as foreign, resulting in an attack and destruction by the body’s own immune
system. These diseases are all characterized by an extremely permeable intestinal wall,” says Dr. Fasano. “We already knew that there was a
distinct connection between an increase in zonulin levels and an increased permeability of the intestines. With this study, we’ve been able to
identify a way to prevent zonulin from causing leakage from the intestines as it does in people with these autoimmune diseases.”
With funding from the National Institutes of Health, Dr. Fasano and his research team used diabetes-prone rats to test the effectiveness of a
zonulin inhibitor peptide called AT-1001, which is known to prevent zonulin from regulating intestinal permeability. The peptide prevented the
development of diabetes in the vast majority of the animals tested. Only 27 percent of those that were given water containing AT-1001
developed diabetes. “In essence, we saw that this peptide stopped the sequence of events that leads to diabetes,” Dr. Fasano says.
Dr. Fasano adds that this significant discovery could eventually lead to the development of an oral medication to arrest autoimmune diseases
in the early stages. Immediate plans call for clinical trials to test the use of AT-1001 in patients with celiac disease. Alba Therapeutics, a
Baltimore-based biopharmaceutical company, has already sought approval from the FDA to conduct those trials.
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