industry & policy
Beating Alzheimer’s
Why we desperately need to find new treatments
for one of Australia’s biggest killers.
Dr Bill Ketelbey
O
f all the diseases affecting the brain, Alzheimer’s disease
is one of the most challenging. We are not much further
along in our understanding of the cause and progression
of the disease than we were 100 years ago when it was first
identified by Dr Alois Alzheimer.
Alzheimer’s begins with mild cognitive impairment – a decline
in brain functions related to memory, the ability to recall particular
words, or to make decisions. The cognitive changes occur
because the neurons, the cells that transmit signals around the
brain, degenerate and die, particularly in the hippocampus and
the frontal cortex. These regions of the brain control memory,
regulate emotion, behaviour and language, and play an important
role in the development of our personality.
Why do the neurons die? Despite decades of research, it’s still
not clear. However, the brains of patients with Alzheimer’s are
littered with abnormal clumps of a protein called β-amyloid,
which blocks communication between the neurons. Without
this essential link to other neurons, they die. In the absence of
any other major clues about the development of Alzheimer’s, the
‘amyloid theory’, as it’s become known, has dominated Alzheimer’s
research for the last 30 years.
My involvement with Alzheimer’s disease research began with
the development of the drug Aricept. Approved in the late 1990s,
Aricept was the first really effective Alzheimer’s treatment. Since
then only three other drugs have been approved for patient use.
All of them, including Aricept, provide only temporary relief of
the symptoms of Alzheimer’s, and none of them prevent further
damage to the brain. For many patients, the drugs become
ineffective within a year.
Alzheimer’s is the second most common cause of death in
Australia behind heart disease. It affects one in 10 Australians over
65, and the number affected by Alzheimer’s is expected to double
every 20 years.
More recently, studies have revealed that the Alzheimer’s disease
process begins at least 10 years before the symptoms appear, and
that the build-up of β-amyloid may be a sign, not the cause, of
the disease. Research drugs targeting β-amyloid may have failed
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because they act too late to make a real difference, or perhaps
because they aren’t targeting the most important pathway in the
disease process. Broadening our focus away from β-amyloid and
intervening earlier in the disease may be the way forward.
One potential early treatment target that shows great promise
is the hormone cortisol. There is growing evidence that shows a
strong association between persistently raised cortisol levels in the
blood and brain and the development of Alzheimer’s. Reducing
excess cortisol in the brain presents a promising new approach.
Actinogen Medical, an Australian biotechnology company, and
Edinburgh University in Scotland have developed Xanamem, a
drug that does precisely that – reduce excess cortisol production
in the hippocampus and frontal cortex.
Actinogen Medical is currently conducting XanADu, a large
international clinical trial assessing the effectiveness and safety of
Xanamem in patients with mild Alzheimer’s disease. Details on the
trial, including the study design and the locations, can be found on
www.clinicaltrials.gov, with the identifier NCT02727699.
So, what draws me to Alzheimer’s research? The huge unmet
medical and societal need for new effective treatments is a
powerful motivation. We urgently need further research into the
underlying causes of Alzheimer’s and more investment in bringing
new drugs to market. As someone with a family member suffering
from Alzheimer’s, I also have a personal reason to continue
searching for answers to combat this awful disease.
We are making excellent progress. Even though hundreds of
research drugs have failed in clinical trials, each failure provides us
with new insights. Recent advances in brain imaging technology
have allowed us to monitor brain function in patients to a level
of detail unimaginable even three years ago. This technology
may allow us to detect the early signs of Alzheimer’s well before
the symptoms appear, and at a point where drugs may be more
effective in slowing down or preventing the brain’s degeneration.
There’s now an optimism in the research community that we are
on the threshold of some major advances in treatment.
Until then, there is much to do. There have been remarkable
improvements in the prevention of cardiovascular disease and
treatment of cancer, achieved with a global approach and the
support of government and the community. We need to apply the
same strategy to our war on Alzheimer’s disease. ■
Dr Bill Ketelbey is the CEO of Actinogen Medical.