Huntington's disease is an inherited neurological disease for which there
is no cure. Medications such as antidepressants, sedatives, and low doses of
antipsychotics are used to treat its psychological symptoms but are palliative
Now, a possibly effective treatment for the memory impairments of
Huntington's may have been found. It is a compound called an ampakine.
The research on this compound was headed by Gary Lynch, Ph.D., a professor
of psychiatry and human behavior at the University of California, Irvine.
Results were published online March 5 in the Proceedings of the National
Academy of Sciences
Levels of a brain protein called brain-derived neurotrophic factor (BDNF)
are known to be abnormally low in the brains of those with Huntington's
disease. These abnormally low levels are also suspected of contributing to the
memory deficits in Huntington's patients. If lab mice are genetically
engineered to contain the defective gene that causes Huntington's, they
develop symptoms similar to those of Huntington's patients and thus serve as
models for studying the disease.
So Lynch and his colleagues decided to see whether ampakines, a class of
drugs that increase the transmission of glutamate in the brain and thereby
increase levels of BDNF, might have an effect on the memory of mice
genetically engineered to have Huntington's.
Lynch and his coworkers studied three groups of 16-week-old mice in their
experiment. There was a minimum of 15 mice in each group. One group was a
normal type that got placebo injections; a second group was a Huntington's
type that got placebo injections, and the third group was a Huntington's type
that got ampakine injections. The animals received either a placebo or an
ampakine injection twice daily for four days. They were then given a memory
test 18 hours after each injection.
Compared with the normal mice that got a placebo, the Huntington's mice
that got the ampakine showed the same movement deficits as did the
Huntington's mice that got a placebo. Thus the ampakine appeared to have no
favorable impact on Huntington's movement deficits. However, the Huntington's
mice that received the ampakine showed memory as good as the normal mice that
received a placebo, whereas the Huntington's mice that received a placebo did
not do as well. Thus, the ampakine injections appeared to improve the mice's
"That such a mild drug regimen was effective surprised us,"
Lynch told Psychiatric News. "The ampakine had a half-life of
[only] 15 minutes."
Autopsies of the mice suggested that the ampakine worked by increasing the
BDNF levels in the mice's brains.
Although the particular ampakine used in these experiments has not yet been
tested in humans, other types of ampakines have been tested and found to be
safe, Lynch said. In fact, he added, ampakines are currently being tested in
clinical trials to see whether they can help subjects with sleep apnea or
"Given that ampakines are well tolerated in clinical trials and were
effective in this study after brief exposures, these results suggest a novel
strategy for chronic treatment of the cognitive difficulties that occur in the
early stages of Huntington's," Lynch and his group concluded.
The research was funded by the National Institutes of Health, the
Huntington's Disease Drug Works Foundation, and Cortex Pharmaceuticals
An abstract of "Up-Regulating BDNF With an Ampakine Rescues
Synaptic Plasticity and Memory in Huntington's Disease Knockin Mice" is