New therapeutic molecules show promise in reversing the memory loss
linked to depression and aging. These molecules not only rapidly improve
symptoms, but remarkably, also appear to renew the underlying brain
impairments causing memory loss in preclinical models.
Toronto’s Centre for Addiction and Mental Health (CAMH) show promise in
reversing the memory loss linked to depression and aging.
These molecules not only rapidly improve symptoms, but remarkably,
also appear to renew the underlying brain impairments causing memory
loss in preclinical models.
says Dr. Etienne Sibille, Deputy Director of the Campbell Family
Mental Health Research Institute at CAMH and lead scientist on the
What’s unique and promising about these findings, in the face of many
failures in drug development for mental illness, is that the compounds
are highly targeted to activate the impaired brain receptors that are
causing memory loss, he says.
It took a series of studies the most recent appearing in January 2019 in Molecular Neuropsychiatry
— to reach this stage. First, Dr. Sibille and his team identified the
specific impairments to brain cell receptors in the GABA
Then they showed that these impairments likely
caused mood and memory symptoms in depression and in aging.
The new small molecules were invented to bind to and activate this
receptor target. The idea was that they would exert a therapeutic effect
by “fixing” the impairment, resulting in an improvement in symptoms.
The molecules are chemical tweaks of benzodiazepines, a class of
anti-anxiety and sedative medications that also activate the GABA
system, but are not highly targeted.
A single dose of these new molecules was administered in preclinical
models of stress-induced memory loss.
Thirty minutes later, memory
performance returned to normal levels, an experiment that was reproduced
more than 15 times.
In another experiment involving preclinical models
of aging, memory declines were rapidly reversed and performance
increased to 80 per cent after administration, essentially reaching
levels seen in youth or earlier stages of adulthood. This improvement
lasted over two months with daily treatment.
“The aged cells regrew to appear the same as young brain cells,
showing that our novel molecules can modify the brain in addition to
says Dr. Sibille. He expects to start testing the
molecules in clinical research in two years.
“We’ve shown that our
molecules enter the brain, are safe, activate the target cells and
reverse the cognitive deficit of memory loss.”
If successful, the potential applications are broad. Not only is
there a lack of treatment for cognitive deficits in mental illness, but
the brain improvements suggest the molecules could help to prevent the
memory loss at the beginning of Alzheimer’s disease, potentially
delaying its onset.
Centre for Addiction and Mental Health