New Drug Targets Liver and Pancreas
Researchers said on Thursday they had
found a new class of drugs that might attack diabetes
on more than one front -- and that could be taken
as a pill.
They have only tested the drugs in rats and mice
so far, meaning years of development are needed,
but said the medications could offer an alternative
to some of the drugs that many diabetes patients
must take.
"At this point in time, this type of drug
will not allow us to replace insulin," cautioned
Joseph Grippo, a vice-president at Swiss drug
giant Roche who led the research. The drug is
targeting type-II diabetes populations before
they get to insulin.
Patients with type II diabetes make too little
insulin and have too much glucose in their systems.
The new compound stimulates the pancreas to release
more insulin and keeps the liver from producing
too much glucose. Diabetes patients often take
two drugs for this -- sulfonylureas and metformin.
Roche's drug, known by the experimental name RO-28-1675,
is a glucokinase enzyme activator. It acts on
GK, an enzyme that diabetes researchers have known
about for years.
The glucokinase enzyme is the body's first step
in breaking down or metabolizing glucose.
"When the enzyme is functioning normally,
GK helps the body maintain glucose levels by controlling
the release of insulin from the pancreas as well
as the disposal of glucose in the liver."
HOPES FOR HUMAN TESTS WITHIN A YEAR
In 1992 researchers discovered a mutation in the
GK gene caused a certain type of diabetes called
maturity onset diabetes of the young type 2. But,
it did not seem like a good target for a drug.
"In order to make it effective you have to
activate the enzyme. If you look at many of the
drugs out there the activators are rare. Most
drugs inhibit enzymes.
But when Roche scientists started screening through
a library of compounds -- a common way to look
for drugs -- they found one that seemed like it
would activate GK.
Reporting in the journal Science, they said it
worked both in lab dishes and in mice.
Grippo said they hope to get approval to start
testing it in people within a year.
"There have not been that many new drugs
for the treatment of diabetes ever discovered,
and this one is unique in its mechanism of action,"
said Mark Magnuson, a researcher at Vanderbilt
University in Nashville, Tennessee who worked
with GK for years.
"No one ever thought we would find a drug
that directly targets the enzyme and activates
it," Magnuson added in a statement.
One big question is whether early treatment with
drugs can prevent the development or progression
of type-II diabetes. A class of drugs called TZDs
or glitazones, which includes GlaxoSmithKline's
Avandia, are being tested with prevention in mind.
Grippo said the new Roche drug would not compete
with these drugs, but said its mechanism of action
might help prevent the deterioration of the pancreatic
cells that produce insulin.
"If we catch people early enough, it will
possibly have some benefit," Grippo said.
"It's something we will look for."
