* Ebselen works like lithium in mouse study
* Standard treatment lithium discovered 60 years ago
* Scientists say new drug could have fewer side effects
By Kate Kelland
LONDON, Jan 8 (Reuters) - A drug for bipolar disorder that
works like lithium - the most common and effective treatment -
but without lithium's side-effects has been identified by
British researchers in tests on mice.
Scientists say the drug, ebselen, may be a swift answer to
long-sought after better medications for patients with the manic
depressive disorder, since it is already known to be safe.
If the drug could be "repurposed" and licensed for the
treatment of bipolar disorder, it could reduce the unpleasant
side effects of weight gain, thirst and potential kidney damage
that patients risk when taking lithium.
"Ebselen is an experimental drug that has been tested in
people for other conditions, and does not have problematic side
effects like lithium does," said Grant Churchill of the
department of pharmacology at Britain's Oxford University.
Bipolar disorder effects around 1 percent of the population
worldwide and sufferers can experience moods that swing from one
extreme to another, and have periods of depression and mania
lasting several weeks or longer. These high and low phases are
often so extreme they interfere with everyday life and work.
In a telephone interview Churchill said that in tests, his
team found that mice who were made manic with small doses of
amphetamines were able to be calmed again with ebselen.
"In mice, ebselen works like lithium," Churchill said. "Now
we urgently need to see if it works like lithium in people."
Some 60 years after it was first discovered, lithium - a
mood stabiliser that can protect against both depression and
mania, and reduce the risk of suicide - remains the most
effective long-term treatment.
But it is very toxic - at only twice the right dose it could
kill a patient, Churchill said - and its adverse side-effects
mean many people stop taking the drug and relapse into episodes
of mania and depression.
Churchill worked with Sridhar Vasudevan to filter through a
library of existing drugs - the U.S. National Institutes of
Health Clinical Collection - that are considered safe but do not
currently have a proven use.
They screened the library for any drugs that blocked an
enzyme that is key to lithium's success and found ebselen was a
possible lithium mimic.
"This is one of the first handful of examples of drug
repurposing, where a new use has been found for an existing
drug," Vasudevan said.
Ebselen is an antioxidant originally developed up to late
stage, or phase III, clinical trials by the Japanese firm
Daiichi Sankyo for the treatment of stroke, but which
never reached market and is now out of patent.
Vasudevan said his study, reported in the journal Nature
Communications, showed ebselen had the same or similar action as
lithium in the brains of mice, blocking the same enzyme.
The researchers are a now starting a small study in healthy
human volunteers to look for effects on brain function. If that
shows ebselen has similar effects to lithium, they plan to move
to second stage trial in bipolar patients.
(Editing by Pravin Char)