Gene therapy cures Type 1 diabetes in mice
4 July 2011
An experimental gene therapy cure for Type 1 diabetes has had
a nearly 80% success rate in curing diabetic mice. The results offer
possible hope of curing a disease that affects millions of people around
“With just one injection of this gene therapy, the mice remain
diabetes-free long term and have a return of normal insulin levels
in the body,” said Vijay Yechoor, MD, the principal investigator and
an assistant professor at Baylor College of Medicine in Houston.
Yechoor and his co-workers used their new gene therapy in a
non-obese mouse model of Type 1 diabetes. The therapy attempts to
counter the two defects that cause this autoimmune form of diabetes:
autoimmune attack and destruction of the insulin-producing beta
cells by T cells.
First, the researchers genetically engineer the formation of new
beta cells in the liver using neurogenin3. This gene defines the
development of pancreatic islets, which are clusters of beta cells
and other cells. Along with neurogenin3, they give an islet growth
factor gene called betacellulin to stimulate growth of these new
The second part of the therapy aims to prevent the mouse’s immune
system from killing the newly formed islets and beta cells.
Previously the research team combined neurogenin3 with the gene for
interleukin-10, which regulates the immune system. However, with
that gene, they achieved only a 50 percent cure rate in diabetic
mice, Yechoor said.
In the new study, the investigators added a gene called CD274 or
PD-L1 (programmed cell death 1 ligand-1). It inhibits activity of
the T cells only around the new islets in the liver and not in the
rest of the body, he explained.
“We want the gene to inactivate T cells only when they come to
the new islet cells. Otherwise, the whole body would become
immunocompromised,” Yechoor said.
This treatment reversed diabetes in 17 of 22 mice, or 78%.
Diabetic mice that otherwise live only six to eight weeks were
growing normally and were free of diabetes as long as 18 weeks after
injection of the gene therapy, Yechoor said.
This treatment approach, he said, “has the potential to be a
curative therapy for Type 1 diabetes.”
The other mice reportedly responded to the gene therapy initially
but then became diabetic again. There are two possibilities,
according to Yechoor, why the therapy did not achieve a 100% cure
“T cells are the predominant part of islet destruction, but other
pathways, including beta cells could also contribute, meaning we
would need to target those pathways as well,” Yechoor said. “Or
maybe the efficiency of this new protective gene is not sufficient,
and we need to give a larger dose.”