Professor Ashley Bush
Florey Institute of Neuroscience and Mental Health
15 September 2017

By 2036, the total cost of dementia is predicted to increase by 81 per cent to $25.8 billion in Australia1

Finding treatments for the most common form of dementia—Alzheimer’s disease—has proved almost impossible. However, after decades of research a new treatment could offer patients a way to slow this debilitating disease.

Professor Ashley Bush and his team at the Florey Institute of Neuroscience and Mental Health are about to start a clinical trial testing the effects of a drug that removes excess iron from the brain.

Professor Bush and his team have established that an elevation of iron in the brain seems to contribute to the damage that is occurring in Alzheimer’s disease.

‘What we found in our most recent study—using MRI and PET scanning of the brain was that it is not enough to have amyloid [abnormal clusters of protein fragments that build up between nerve cells]; you also have to have elevated iron. If your iron levels go beyond a certain level then the brain cannot tolerate the presence of the amyloid,’ Professor Bush said.

‘It has always been a mystery with Alzheimer’s as to why everyone with the disease has got amyloid in the brain but not everyone with amyloid has got Alzheimer’s disease.

‘The question then becomes, what would happen if you could lower the iron in the brain with a drug?’

While Professor Bush’s team in Melbourne were working hard on Alzheimer’s disease, a group in France, led by Professor David Devos, published two clinical trials in the treatment of Parkinson’s disease—another debilitating form of dementia—using a drug to lower brain iron.

‘It was very encouraging and suggested that lowering brain iron could be therapeutic,’ Professor Bush said.

‘We thought we can do the same thing in Australia but let’s do it for Alzheimer’s disease since we have the expertise.’

One of the lessons learned from this research is that there is no excretion mechanism in the body for iron. The only way to remove it is by using a drug that pulls it out of the body.

Deferiprone is a drug currently used for the treatment of iron overload disorders and will be used in this trial (Deferiprone to Delay Dementia—The 3D Study) to see if it slows the progression of the disease.

‘The 3D trial is extremely exciting because for the first time we will be able to assess someone’s risk of progressing into cognitive decline without needing to perform invasive and costly tests. We will also be testing a compound that may prevent or slow the natural course of the disease,’ Professor Bush said.

‘We will take their base-line cognitive performance and then we will see what it is like 12 months later. If we see an improvement in that 12 months that is similar in its dimension to current/existing treatments—drugs that stimulate what you have left—we will say that is clinically significant. We are hoping for more than that.

‘If the 3D trial results prove that low iron slows disease progression, we imagine a future where your GP sends you off for your 60-year health check, including a brain iron MRI scan, which is quick, cheap and painless. If you have high brain iron, then we would order an amyloid PET scan. Once we had those two measurements, we could predict the likely onset of Alzheimer’s and begin you on therapy to lower the iron, and delay disease onset.

'This will be a major turning point for a few different forms of neurodegenerative disease.'

This NHMRC project grant provides Dr Bush and the team the chance to test 171 people in a randomised placebo controlled trial.

This type of grant helps to create new knowledge by funding the best investigator-initiated research project plan between one and five years in any area relevant to human health.

‘If the clinical trial is successful, the drug could be used in the clinic. I would think it’s somewhere between four to eight years before we would see this out there getting used regularly,’ Professor Bush said.

With a rapidly aging population set to reach 5.5 million people aged 85 plus by 21012, Alzheimer’s disease is set to become an epidemic.

Currently Alzheimer’s affects over 413,000 Australians—about five per cent of people over the age 65 and rises to at least 25 per cent of people over the age of 80.

‘Alzheimer’s is not a normal part of ageing,’ said Janice Besch, Director of NHMRC National Institute of Dementia Research.

‘Alzheimer’s physically attacks your brain. The brain of a person with Alzheimer’s is so damaged it weighs 140 grams less than a healthy brain. That’s about the size of an orange.’

‘Given we are dealing with such a complicated disease, with such devastating effects for people with dementia, their families and carers, and bringing such great costs to the economy and society, it is critical that both the public and private sectors work together to find a cure. It is just too big a problem to face without collaboration.’

Australia however, according to Professor Bush ’is punching above our weight’ when it comes to Alzheimer’s research, with leaders in amyloid intervention research.

‘The teamwork that is involved in Australia is exceptional. Australia is amazing at how it manages to produce this type of research with the sort of quality and much less money per capita,’ said Professor Bush.

‘Australia has done well to support large research—big scale academic research involving dozens of investigators and that is really what is needed for us to tackle a very difficult disease.’

NHMRC National Institute for Dementia Research (NNIDR) is a key element of the Australian Government’s $200 million initiative to boost dementia research. NNIDR targets, coordinates and translates the strategic expansion of dementia research in Australia.

NNIDR collaborates with Australia’s best researchers while also drawing on the expertise of consumers, health professionals, industry and policy makers to translate evidence into policy and practice.

Through collaboration, including with international partnerships, NNIDR intends to make a significant contribution to the international priority set by the World Dementia Council: to achieve a five-year delay in the onset of dementia by 2025.

1The National Centre for Social and Economic Modelling NATSEM (2016) Economic Cost of Dementia in Australia 2016-2056