Scientists at The Scripps
Research Institute (TSRI) have performed successful tests of an
experimental methamphetamine vaccine on rats. Vaccinated animals that received
the drug were largely protected from typical signs of meth intoxication. If the
vaccine proves effective in humans too, it could become the first specific
treatment for meth addiction, which is estimated to affect 25 million people
worldwide.
“This is an early-stage study,
but its results are comparable to those for other drug vaccines that have then
gone to clinical trials,” says Michael Taffe, an associate professor in TSRI’s
addiction science group, known as the Committee on the Neurobiology of
Addictive Disorders. Taffe is the senior author of the study, which is
currently in press with the journal Biological Psychiatry.
A Common and Dangerous Drug of
Abuse
Over the past two decades,
methamphetamine has become one of the most common drugs of abuse around the
world. In the U.S. alone there are said to be more than 400,000 current users,
and in some states, including California, meth accounts for more primary drug
abuse treatment admissions than any other drug. Meth has characteristics that
make it more addictive than other common drugs of abuse, and partly for this
reason, there are no approved treatments for meth addiction.
In recent years, scientists at
TSRI and other institutions have taken the innovative approach of developing
vaccines against addictive drugs. These vaccines evoke antibody responses
against drug molecules, just as traditional vaccines evoke antibody responses
against viruses or bacteria. Anti-drug antibodies are meant to grab hold of
drug molecules and keep them from getting into the brain — preventing the drug
from giving the user a high and removing the incentive for taking the drug.
Vaccines against nicotine and
cocaine are already in clinical trials. Some meth vaccines have been tested in
animals, but generally with unpromising results. The methamphetamine molecule
is structurally simple, making it relatively unnoticeable to the immune system.
Meth and its main metabolite, ordinary amphetamine, also tend to linger once
they get into the nervous system, so that even a little drug goes a long way.
“The simple structure and long half-life of this drug make it a particularly
difficult vaccine target,” says Kim Janda, professor of chemistry at TSRI.
‘Encouraging Results’
Two years ago Janda and his
laboratory developed six candidate meth vaccines. In each, the main active
ingredient was a chemical cognate of the methamphetamine molecule — that
otherwise would be too small to evoke any antibody response — linked to a larger,
antibody-provoking carrier molecule. Early tests in mice indicated that three
of these vaccine candidates could evoke a strong antibody response to meth.
Taffe’s laboratory later tested these three vaccines in rats and found the one,
designated MH6, that worked best at blocking two typical effects of meth — an
increase in physical activity and a loss of the usual ability to regulate body
temperature.
In the new study, members of
Taffe’s laboratory, including Research Associate Michelle Miller, who was lead
author of the study, investigated the MH6 vaccine in more depth. Using a
different experimental setup, they found again that it prevented a rise in body
temperature and burst of wheel-running hyperactivity that otherwise occur after
meth exposure. Underlying these promising effects on behavioral measures was a
robust antibody response, which in vaccinated rats kept more of the drug in the
bloodstream and out of the nervous system, compared to control rats. “These are
encouraging results that we’d like to follow up with further animal tests, and,
we hope, with clinical tests in humans some day,” says Miller.
“I think that this vaccine has
all the right features to allow it to move forward in development,” says Janda.
“It certainly works better than the other active vaccines for meth that have
been reported so far.”
The Next Big Challenge
A separate group of researchers
has reported promising animal test results for an antibody-based treatment. In
this approach, the anti-meth antibodies are grown in cultured cells using
standard biotechnology methods and then injected into the animal in a
concentrated dose, preventing a meth high. Antibody-based therapies are
commonly used to treat cancer and chronic immunological conditions. But they
are typically expensive, costing thousands of dollars per dose, and the effects
of a dose last for a few weeks at most. A meth treatment probably would have to
be much more cost-effective to be widely useful, as addicts frequently have
little money and no health insurance and receive their treatments from
government health services.
In principle, an active vaccine
would be cheap to make and administer and would confer protection for months
per dose, rather than weeks with conventional monoclonal antibody therapy. In
practice, active meth vaccine candidates don’t yet last that long; for example,
the MH6 candidate in the current study was given in four doses over 12 weeks.
But Janda and Taffe believe that with further adjustment, an active meth
vaccine could sustain an anti-meth antibody response for a much longer period.
“Extending the duration of
protection is the next big scientific challenge in this field,” says Taffe.
The Scripps Research Institute
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