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Q&A with Professor Greg Anderson

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Q&A with Professor Greg Anderson

Professor Greg Anderson

is Group Leader of #QIMRBerghofer’s Iron Metabolism Laboratory and is one of Australia’s leading authorities on haemochromatosis.

Please explain your area of research at QIMR Berghofer

My group is interested in all aspects of the biology of iron and iron-related diseases. Body iron levels must be kept within defined limits, so having too little (iron deficiency) or too much (iron overload) can have significant clinical consequences. We have had a long-term interest in the iron loading disease hemochromatosis, and our studies in this area have included investigations into the population prevalence of the disease, its clinical presentation, the consequences of various therapies and the basic molecular mechanisms that explain why people with haemochromatosis accumulate too much iron. A major part of this has been a detailed exploration of the mechanisms by which the body absorbs iron from the diet.

During World Haemochromatosis Week, can you tell us some of the key facts people should know about the disorder?

Haemochromatosis is the commonest genetic disease in Australia. It is almost exclusively a disease of Caucasians, and the disease appears to have originated in northwest Europe.

People with haemochromatosis absorb too much iron from their diet. Normally, if a person gets too much iron, the body will respond to that by preventing more iron entering. In haemochromatosis, this process does not work very efficiently, so people continue to absorb iron even though they have excess in their body.

The earliest sign of haemochromatosis is often excessive tiredness, and interestingly this is often the first sign of iron deficiency.

If untreated, iron can accumulate to quite high levels in multiple tissues and can damage the liver, heart, pancreas and pituitary gland.

The key to managing haemochromatosis is early detection and treatment. This is because treatment for most people is straightforward, so if patients are detected early and treated, then they do not suffer from any of the adverse consequences of haemochromatosis

How is haemochromatosis treated and what are the future prospects in this area?

Since most iron in the body is in the red blood cells, the most efficient way to remove iron from a patient with haemochromatosis is through bleeding.

The blood removal strategy has two phases. The first phase consists of very aggressive bleeding to remove accumulated iron from the body. A person with 20g of extra iron will need to be bled approximately 80 times. This is the equivalent of giving a blood donation one a week for about 18 months. The second phase of blood remove is called the maintenance phase. Patients will be bled approximately once every three months to keep their iron levels low.

The blood removed from haemochromatosis patients is very safe and can be given to others in need, e.g. for blood transfusions.

Occasionally there may be reasons why it is not possible to bleed a patient. In this case, there are some very effective drugs that can be used to bind iron and facilitate its excretion from the body.

Multiple drug strategies are being investigated to limit the amount of iron absorbed from the diet, and a number of these are now in clinical trials. Research carried out at QIMR Berghofer on how iron absorption is regulated laid the foundation for a several of these new approaches. Drugs like these will not remove iron from the body, but they potentially will be able to prevent the need for maintenance phlebotomy.

Please tell us about some of your recent research findings and how they are significant.

People with haemochromatosis frequently develop cirrhosis of the liver and are at high risk of developing liver cancer if they are not treated early to remove the iron. It was previously thought that patients who already had severe liver disease might not benefit from treatment because their liver was already too damaged. However, some of our recent work has shown that even patients with advanced liver disease can benefit from iron removal and this reduces their risk of developing liver cancer later in life.

It is also been known for some time that patients with haemochromatosis have a variable presentation. Some accumulate a great deal of iron, but others accumulate very little. Sometimes there are clear reasons for this. For example, a regular blood donor will not accumulate so much iron as they are effectively treating themselves. In other cases, the reasons are not so clear. We have shown that genetics is important, and that some people have particular genetic variants that either prevent them from absorbing excess iron or promote it. We have identified a number of these genetic variants and are working to understand how they contribute to the severity of haemochromatosis.

How does your research help people and clinicians?

Our research has helped our understanding of haemochromatosis in a number of ways. It has:

  • provided a clear picture of just how common haemochromatosis is in Australia and shown that men are far more likely to be more severely affected than women;
  • shown the clinical importance of iron removal in limiting the more severe consequences of haemochromatosis;
  • demonstrated that even a mild elevation of iron in the body can be clinically significant, thus underlying the importance of regular treatment;
  • identified genetic variants that can help determine whether patients are more likely to develop severe iron loading; and
  • provided a greatly enhanced understanding of the molecular mechanisms underpinning the development of haemochromatosis. This information has also proved extremely useful in understanding the pathogenesis of related diseases and has laid the basis for a new range of therapeutic opportunities to treat haemochromatosis.
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