Scientists
at Yale University have developed the first
practical method to create a compound called huperzine A in the laboratory. The
compound, which occurs naturally in a species of moss found in China, is an enzyme inhibitor that has been used
to treat Alzheimer’s disease in China
since the late 1990s and is sold in the U.S. as a dietary supplement to
help maintain memory. Scientists believe it could also potentially combat the
effects of chemical warfare agents.
Until
now, researchers have only been able to derive small amounts of the compound
directly from the Huperzia serrata plant, or had to resort to lengthy
and cumbersome methods to synthesize it in the laboratory.
Now
researchers at Yale have developed a practical and cost-effective method to
synthesize huperzine A in the laboratory. The process requires just eight steps
and produces a yield of 40%. Previously, the best synthetic techniques had
required twice as many steps and achieved yields of only 2%.
“Being
able to synthesize large amounts of huperzine A in the laboratory is crucial
because the plant itself, which has been used in Chinese folk medicine for
centuries, takes decades to grow and is nearing extinction due to
overharvesting,” says Seth Herzon, the Yale chemist who led the research,
which is described in Chemical Science.
In
some places, huperzine A can cost up to $1,000 per milligram. Herzon and his
team produced several grams of the compound in their laboratory and are capable
of creating much more. They believe they will be able to drive the cost down to
just 50 cents per milligram, and have partnered with an industrial firm to help
produce it on larger scales.
The
firm plans to comprehensively evaluate the therapeutic potential of huperzine A
by conducting clinical trials for several different neurological disorders in
the U.S.
In addition, the Herzon laboratory and the firm are working with the U.S. Army,
which is interested in huperzine A’s potential in blocking the effects of chemical
warfare agents, he says. The compound has been shown to protect primates
against chemical warfare agents, without side effects.
Other
Alzheimer’s treatments based on enzyme inhibitors are currently prescribed in
the U.S.,
but huperzine A binds better, is more easily absorbed by the body and last
longer in the body than other treatments, Herzon says.
“We believe huperzine A has the potential to
treat a range of neurologic disorders more effectively than the current options
available,” Herzon says. “And we now have a route to huperzine A that
rivals nature’s pathway.”
Filed Under: Drug Discovery
