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Dr Bill Ketelbey. Image: Supplied.

Why we need new treatments to beat Alzheimer’s

Of 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 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 chief executive of Actinogen Medical.

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