News for Type 2’s
ASSOCIATED PRESS
Feb. 3, 2000 A technique that allows insulin hormone to be stored in cells
and then released as needed by a pill eventually may offer a treatment for
diabetes that does not require daily injections, researchers say.
THE EXPERIMENTS, thus far, have been performed only on mice, but researchers
say a system using an implanted insulin gene may be ready for human testing
within two years.
In a study to be published Friday in the journal Science, researchers at
Ariad Pharmaceuticals in Cambridge, Mass., and at Memorial Sloan-Kettering
Cancer
Center in New York said the cell engineering technique was able to control
diabetes in a group of laboratory mice and is now being tested on larger
animals.
Tim Clackson, senior author of the study, said that the technique causes
insulin, or some other protein, to clump inside a cell with another protein,
forming a molecule that is too large to leave the cell. A drug, given as a
pill, breaks up the clump, allowing the insulin to flow into the bloodstream
in a way that mimics the spurt of hormone normally secreted by the pancreas.
The amount of protein (such as insulin) that gets released is directly
related to the amount of drug that is given, said Clackson. The more
drug you give, the more protein gets released into circulation.
In diabetes, the technique theoretically would allow a patient to precisely
control insulin levels in the blood by a pill. Many diabetics now must
control insulin levels by injection.
A common type of diabetes is caused by the failure of the pancreas to
produce an appropriate amount of insulin to metabolize glucose, or
sugar, levels in the blood stream. Normally, the pancreas releases
insulin in response to the detected level of glucose.
CLEVER SCIENCE
Dr. Richard Furlanetto, scientific director of the Juvenile Diabetes
Foundation, said the experimental technique =93is very clever science but
might fall short.
To be truly useful, it would have to be coupled to a system that would
release the hormone in direct response to the levels of glucose in the
blood,
said Furlanetto.
However, Furlanetto said the technique could be very useful in treating
conditions that require periodic secretion, or pulsed release, of some
needed protein, such as growth hormone.
In the experiment, Clackson and his colleagues inserted into laboratory
cells genes that produce insulin and a protein that naturally clumps, or
aggregates, with insulin. Once inside the cells, the genes produce the two
proteins. They form clusters that are too large to pass through pores in the
walls of the cell compartments.
The engineered cells were then injected into the muscles of mice that are
diabetic and normally develop high levels of glucose in the blood.
When these mice were fed a drug that caused the protein clusters to split
apart, insulin was released into the bloodstream and glucose levels dropped
to normal.
In control mice, which had the engineered cells but were not given the oral
drug, insulin did not appear in the bloodstream and glucose levels stayed
high.
The insulin stays in the compartments of the cell and has no toxicity or
adverse effects. It just sits there, said Clackson. Only when the
animal receives the drug do the aggregates break apart and then flow
into the circulation.
Clackson said the experiment was only a proof of concept for the
technique. The next step is to transfer genes directly into body muscle
cells, a common gene therapy technique. To do this, the target genes
will be put into a virus that would be injected and deliver the genes into
muscle cells, he said.
Although the initial target of the research is diabetes, Clackson said the
protein clustering technique could also be used to deliver any protein that
the body needs in spurts. For instance, the technique could be used to
administer growth hormone, or proteins that would provide pain relief,
appetite control or correct brain chemistry, he said.