Wednesday, 5/28/97 Researchers develop potential treatment for
juvenile diabetes Therapy involves producing protein with ability
to halt disorder at lower cost
By Kathryn Combs Daily Bruin Contributor Diabetes in any form
can be one of the most debilitating and devastating diseases,
especially when developed during childhood. In the United States
alone, there are approximately 800,000 cases of juvenile diabetes.
Those afflicted with the disease are often faced with major
lifestyle changes and lifelong insulin therapy. However, due to a
recent discovery by UCLA molecular biologist Daniel Kaufman and
associates, alternate therapies may slow the onset of juvenile
diabetes, if not ultimately prevent it. In collaboration with
Genzyme Transgenics, a biotechnology company specializing in the
production and development of biopharmeceuticals, researchers have
devised a way to produce the protein glutamic acid decarboxylase
(GAD) in the milk of laboratory mice. Animal studies have shown
that this protein, when taken orally, has the potential to halt the
autoimmune process that leads to the onset of insulin-dependent
diabetes mellitus (IDDM), also known as Type 1 or juvenile
diabetes. "GAD is potentially the most effective molecule that
could be developed for the oral tolerization of Type 1 diabetes,"
said Kaufman, of the UCLA Institute of Molecular Biology.
"(However) even though we are molecular biologists, this protein is
very hard to make and (is) difficult to produce in large amounts,"
he added. The production of the protein GAD in the milk of mice is
significant because the protein is known as a nonsecreted protein,
usually residing within the cells that produce it. Thus,
traditional methods of protein cultivation would be costly. The
ability to have mice produce this protein in their milk saves
costs, and researchers hope to apply this technique to animals that
quickly mature and are able to produce larger quantities of milk.
Dr. Allan Tobin, director of the Brain Research Institute,
explained the possible effects of this discovery on the therapy now
offered for Type 1 diabetes. "This may actually lead to the
prevention of juvenile diabetes," Tobin said. "There is evidence in
mice that oral tolerance can prevent diabetes. Until now, the
problem has been that it is very expensive to make enough GAD," he
said. "The market price of GAD is about $1,000 per milligram, (so)
now that we can get mice to secrete GAD in their milk, the next
step is to get rabbits to," Tobin continued. According to Kaufman,
for this method of oral tolerance to be applied to humans, several
milligrams per week must be administered. Although the human trials
have not yet begun, researchers are hopeful about the potential
benefits of the therapy. "There has yet to be an case of this
working in humans; (however), oral therapy is very attractive for
children as opposed to vaccination as a therapy for suppressing
autoimmune responses," Kaufman said. "There is so much evidence
from animal models. We think that its just a matter of working out
the details," he added. "Juvenile diabetes is a major problem among
children, and the possibility that we may be able to prevent or
reduce the severity would have a major impact on health care for
children," said Dr. Edward McCabe, professor and executive chief
with the UCLA department of pediatrics. "The goal here is analogous
to getting allergy shots to reduce the reaction. The goal here is
to create a tolerance to this antigen, the GAD protein. "If you can
block the body’s response to this antigen, then you can delay or
prevent the onset of diabetes," McCabe concluded. PATRICK LAM/Daily
Bruin Holding a potential key to diabetes are Daniel Kaufman, Lori
Hanssen, Angelica Olcott, Iona D’Angelo, Blake Middleton and Mike
Bauer. Previous Daily Bruin story: Health problems do not spell
doom for sick