clinical focus
Alzheimer’s breakthrough
Researchers reverse memory
decline in ‘ground-breaking’
Alzheimer’s trial.
By Wade Zaglas
Two scientists at Macquarie
University have discovered a new
treatment that can reverse the
effects of memory loss associated with
Alzheimer’s disease, the leading cause of
death for women and the second leading
cause of death of all Australians.
The “ground-breaking” treatment
developed by the scientists – who happen
to be brothers – reversed the effects of
memory loss related to Alzheimer’s disease
in a study of mice with advanced dementia.
By activating a “naturally protective
enzyme in the brain called p38gamma,
the scientists were able to eliminate the
toxic effects leading to memory loss”. Not
only has this discovery shown promise
for Alzheimer’s disease, the researchers
believe it could hold potential for treating
other dementia-related diseases, such as
fronto-temporal dementia, which typically
affects much younger people in their 40s
and 50s.
Lars and Arne Ittner from Macquarie’s
Dementia Research Centre have
dedicated more than a decade of their
lives to studying dementia treatments.
The breakthrough for the treatment
apparently came when Arne discovered
that gene therapy was able to replace
a protective enzyme in the brain with
“outstanding impacts on memory in
advanced dementia”.
Arne said increases in Alzheimer’s
disease in Australia are attributable to our
ageing population and highlighted the high
mortality rate.
“Numbers-wise, basic science has
managed to reduce the mortality of
all major diseases – cancer, diabetes,
blood pressure and so forth – but we
are still seeing increases in Alzheimer’s
disease, and so getting into the space
and doing something about it is of
utmost importance.”
In completely reversing memory loss
in mice, the brothers achieved more than
they set out to do in their hypothesis.
Originally, their goal was merely to halt the
deterioration of memory.
“We were completely surprised,”
Lars Ittner said.
“They actually recovered their memory
function and their ability to learn returned.
So, two months after we treated the mice
at very old ages, these mice suddenly
behaved like their normal siblings. We
were really stoked. There is no comparable
therapy out there and no other gene
therapy either.”
Before testing began, the Ittners’
aim was to rebuild the lost enzymatic
memory activity of the mice and make it
more efficient. By researching memory
impairments in mice at advanced stages
of dementia, “they found that activating
p38gamma can modify a protein such that
it prevents the development of Alzheimer’s
disease symptoms”.
As Lars Ittner explained: “The naturally
protective enzymatic activity in the brain is
unfortunately lost the further you progress
down the Alzheimer’s disease track – so
the more memory you lose, the more you
also lose this natural protective effect.”
The “world-first”’ findings will be
published in the September edition of the
journal Acta Neuropathologica, and the
researchers believe their gene therapy
approach to treating Alzheimer’s disease
“has the potential to put Australia on
the map”.
Arne Ittner said that, traditionally,
researchers have had difficulty modelling
dementia experiments as, by the time
the person with dementia or their family
notices any peculiarities, they are “already
quite far down the memory defect lane”.
He believes gene therapy will be “especially
significant” in alleviating this difficulty.
“By its nature, the neurodegeneration is
incredibly slow which is notoriously hard to
study and hard to model,” he said.
“The brain is a black box and some
days we get lucky and get glimpses of
how it functions, and we learn we can
interfere with the mechanism in this black
box. Now we have detailed understanding
of the mechanisms involved down to
the amino acids, which is just quite
unprecedented.”
Professor Dan Johnson, pro vicechancellor
of Research Innovation
at Macquarie University, said they
were “hopeful of realising immediate
local benefits”.
“If all goes well, we may find ourselves
with a clinical trial done at Macquarie
Hospital with this therapy,” he said.
“Macquarie is investing in the uniqueness
of the science and the supporting
intellectual property position.
“A lot of the focus right now is on the
fundamental science breakthrough and this
is clearly a significant achievement. The
next phase takes on an additional level of
complexity, cost and time to deliver.”
The university is currently deciding
the best way to develop the therapy
before commencing a clinical trial. If
the therapy’s success story continues,
the researchers hope the gene therapy
can be commercialised within five to ten
years. According to Johnson some of the
world’s biggest pharmaceutical companies
have already shown interest in the
therapy’s potential. ■
20 agedcareinsite.com.au