The Ausimmune Study

Almost 200 Tasmanians are participating in a Multiple Sclerosis study that reserachers hope will shed more light on the disease.

The Ausimmune Study is being coordinated by Dr Robyn Lucas from the Australian National University.

Dr Lucas has been in Hobart with researchers from the Menzies Research Institute who are about to begin analysing data which will look at environmental and genetic factors influencing the immune system.

She says 80 of those being studied have experienced an early episode which may develop into MS.

"This is really a very unique group of people that we are seeing from the very first inklings that there might be any risk of developing MS so there are very very few studies in the world that have looked at that group of people," Dr Lucas said.

The study is also being conducted in Geelong, Newcastle and Brisbane.

Source: ABC Hobart © 2007 ABC (09/08/07)

"Sclerosis" refers to damage and inflammation of the protective sheet of fatty tissue or myelin which surrounds the nerve fibres of the central nervous system. MS involves temporary or permanent interruption to these nervous signals. Symptoms can include loss of co-ordination, fatigue, numbness and changes in vision. MS is more likely to be diagnosed in young adults between 20 and 40 years old, and it's twice as likely to affect women as men.

New Australian research is providing important information about environmental factors and the development of MS. It has been known for some time that there is a strong latitude related gradient in the occurrence of several auto immune diseases including MS. The Ausimmune study is tracking the occurrence of the first demyelinating episode or FDE, an inflammatory condition in which the myelin is disrupted. Professor Ponsonby and the Ausimmune team of researchers have released some preliminary results which confirm that MS becomes more common as you move further north or south from the equator. Even within Australia the occurrence of MS varies with around 11.9 cases per 100,000 people and 75 per 100,000 in Tasmania. The question is which environmental factors play a part ?, including the role of sunlight and Vitamin D in the development and progression of MS.

MS can impact on numerous aspects of life and one of these is diet. There is yet to be any direct evidence of the role of diet in the development of MS, including risk of MS in countries with high intakes of saturated fats, and lower intakes of polyunsaturated fats. Essential fatty acids including omega 6 and omega 3 are significant in the structure of the brain tissue and myelin sheath, with 1/3 of the myelin sheath is polyunsaturated. Like most chronic conditions, diet and nutritional supplements can be seen as a possible treatment, but the research is unfortunately inconclusive.

One major study on the role of diet in the progression of MS was undertaken by Dr Roy Swank who treated MS patients over a period of 34 years. These patients followed a diet including less than 20g of saturated fats per day, as well as a high intake of polyunsaturated fats. Swank reported lower death rates and lower progression for patients following the "swank diet". An Australian version of this diet has been developed by Dr George Jelinek.

Caroline comments that unfortunately it can be difficult to confirm Swank's research with large population based diet trials. She suggests that a Mediterranean type diet with high levels of antioxidants including monounsaturated and polyunsaturated fats, high fish consumption along with plant based omega 3s including walnuts and linseeds. She also suggests that high levels of vitamin and mineral supplements should be used with caution. They can be expensive, as well as unnecessary for many and can have unforseen impacts on the absorption of other nutrients and can interact with medications. Individuals with MS need to be cautious of restrictive diets which include entire food groups such as gluten or milk free diets. It's always best to check with a dietitian who has experience with diet and MS.

MS can also have nutritional consequences which can impact on the nutrition status of people with MS. Depending on the level of symptoms, energy intake may be affected leading to changes in weight, and one study found poor intake of a range of nutrients including zinc, iron, folate and vitamin D. MS can affect diet in numerous ways by impacting on people's ability to shop and prepare food. Fatigue can also mean a lower intake at meals, with a need for high energy snacks and drinks. MS can affect gut motility so people may suffer early satiety or fullness after a meal, and side effects such as reflux are common as is constipation due to reduced mobility and reduced volume of food.

Medication which are commonly used in MS may have side effects such as nausea, dry mouth and diarrhoea. Caroline suggests that it is important that people with MS or their carers should discuss side effects with pharmacist or GP.

Source: ABC 666 Canberra  © 2007 ABC

Teams of medical scientists worldwide are searching for cures for autoimmune diseases like Type 1 diabetes, Multiple Sclerosis and Crohn’s disease. While this worthy activity progresses, there is a quiet anticipation elsewhere that we may be close to discovering some of the risk factors that cause these devastating conditions.

Australia provides a particularly enticing setting for this research because of the unexplained, but quite strong, latitude-related gradient in the occurrence of several of these autoimmune diseases.

“It’s very exciting,” Dr Robyn Lucas, a Research Fellow at the National Centre for Epidemiology and Population Health, says. “We have all of this data coming in but at this stage can only anticipate what answers might be hidden within it.” The information is trickling in as the study nears the end of three years of fieldwork gathering data on environmental influences on immune disorders, and there are tantalising hints about what it will reveal.

As part of a team of researchers, doctors and nurses around the country, Lucas is studying what is known as a ‘first demyelinating episode’ (FDE) in people in four locations on the eastern seaboard of Australia.

An FDE is an inflammatory condition in which the fatty coating around nerve fibres, known as myelin, is disrupted. About 85 per cent of people who have an FDE will develop multiple sclerosis, one of the most devastating diseases to attack the body’s central nervous system.

After the FDE, it’s difficult to pinpoint how long MS will take to develop or indeed whether it will ever develop at all. Symptoms, which include sensory changes like pins and needles or numbness, speech and cognitive impairment, temporary blindness or paralysis, can range from mild to severe. According to the MS Society of Australia, the number of Australians who suffer from MS is around 15,000. This figure has increased sharply since 1960.

“Our study is focused on the precursors of multiple sclerosis, which is why we are looking at people right after they’ve been diagnosed with an FDE, rather than those who already have MS,” Lucas says. “One of the many reasons for this is that we hope studying FDEs will help us understand why most people who have had an FDE go on to develop MS, when 15 per cent or so do not.”

Environmental factors are thought to play a large part in the onset of an FDE, but exactly what those factors are is not yet well-known.

This study, coordinated by Lucas at ANU and known as the Ausimmune Study, is quantifying for the first time the impact of different environmental forces on the immune system.

Study with latitude
It was once thought that Tasmanians had a high incidence of MS compared to the rest of Australia because Scotland had a high MS rate – and many Scots emigrated to Tasmania.

“But research has shown that a latitudinal gradient in MS in Australia, with lower prevalence in Queensland and higher in Tasmania, persists even if you restrict the analysis only to people with origins in the UK and Ireland,” Lucas says. It is now thought that MS rates may be higher in locations like Scotland and Tasmania, compared to more tropical countries – along with other countries on latitudes closer to the South and North poles – because they have fewer daylight hours and are colder. Ultraviolet radiation (UVR) from the sun may play a significant protective role against the development of an FDE or MS.

“The latitudinal gradient of MS is now well known. MS becomes more common as you move further north or south of the equator. So based on this effect the difference between Hawaii, which is closer to the equator, and Scotland, which is closer to the North Pole, would be marked.”

But is it really down to just sun exposure? The variation between Scotland and Hawaii could be due to differences in the healthcare systems of Scotland and Hawaii that result in more people being diagnosed with MS in the former, compared to the latter. Or it could even be because Scots and people living in Hawaii are relatively genetically different.

The Ausimmune Study was born when it was recognised that a multi-centred, environmental study of the factors contributing to MS was needed to understand the environmental antecedents to the disease. It was also clear that Australia would be the ideal location for a study of this type.

“It is the best location because of the wide variation in latitude, our standardised healthcare system and relative genetic homogeneity,” Lucas says.

The Ausimmune Study is studying a range of environmental factors in participants, including infection history, climate and exposure to sun, diet, exposure to synthetic chemicals and materials, past history of head injury and history of recent stressful life events.

There are currently 598 people participating in the Ausimmune Study of which 232 people have been diagnosed with a FDE, known as ‘cases’. The other 366 participants are ‘controls’, individually matched to a case on age, sex and region of residence in four locations along the eastern seaboard: Brisbane, Newcastle, Geelong and Western Victoria, and Tasmania. By comparing data on environmental exposures between cases and controls, the Ausimmune Study hopes to identify likely causative factors.

There have been few studies that have measured the incidence or prevalence of MS in Australia.

A project undertaken in 1981 found that the number of people who had MS in Brisbane was 11.9 per 100,000. In Tasmania it was 75 per 100,000. Another study, published in 1996, measured the growth in MS incidence in Newcastle and found the number of people affected in the 35 years to 1996 doubled to 2.4 per cent per 100,000 people.

“The marked increase in immune disorders is thought to reflect modern environmental and lifestyle factors rather than diagnosis changes,” Lucas says.

Lucas coordinates the work in each of the study centres, where there is a network of neurologists and radiologists who refer people who’ve had an FDE to the study and nurses who gather data.

Participants are asked to provide a copy of their MRI scan, a blood sample, and undergo physical measurements on the skin, as well as completing an extensive questionnaire covering a wide range of topics, including ancestry, birth order, life sun exposure, places of residence, pet ownership, diet, immunisation and infection history, family history and exposure to chemicals. “This is a lot of information so the data analysis will be lengthy,” Lucas says. “It’ll be a very, very rich data set.” The final data collection for the study is expected to be completed by May 2007. “There’s a real element of excitement and anticipation about what we might find,” Lucas says.

Covering every angle The Ausimmune Study will also be first to measure, on a large population-based sample, viral loads of Epstein Barr virus (the cause of glandular fever) in participants’ blood samples.

“I stress that most people who get glandular fever do not go on to get MS, but it has been well established that people who have MS have a history of these infections more commonly than the rest of the population,” Lucas says. “The early indications in our study are that this is certainly looking like it will be the case in this study population.”

Past studies have looked at antibodies of these viruses in the blood, but the Ausimmune Study is examining both antibodies and blood viral load – how much virus is still left in the blood – and will compare this to the control group.

“We are probably the first to look at antibodies in people who don’t actually have MS, but have experienced this first demyelinating episode, so we feel we may just be on the cusp of something very exciting.”

Other data being collected includes the measurement of cumulative skin damage caused by the sun. This is registered by taking a silicone cast of the back of participants’ hands and rating it out of six for the ‘coarseness’ of the skin cell lines.

“When you’re a baby, your hands are lovely and soft, and have lots of little fine lines in the skin. As you get older and are exposed to more and more sun, you lose the fine lines and they become a lot coarser,” Lucas says. “The silicone casts between a person who has had a lot of sun skin damage and those who haven’t should show up that contrast between fine and coarse lines.”

A spectrophotometer is also used to take a reading of sun exposure on four body sites: the back of the hand and the shoulder for recent sun exposure readings, and the buttock and the inside of the arm to gauge natural pigmentation. “The biological effect of sun exposure is determined by how much pigmentation you’ve got,” she says. “We need to adjust our measures of how much sun people have had for what their skin type is.”

The Ausimmune Study is funded by the National Multiple Sclerosis Society of the US, the MS Society of Australia, and the National Health and Medical Research Council. Lucas has also received a Macquarie Bank MSRA Fellowship to work on the study.

“The study would not be possible without the fantastic support of clinicians, radiologists and study nurses in each region, the participants themselves, Multiple Sclerosis Australia and Multiple Sclerosis Research Australia,” Lucas says.

For more information on the Ausimmune Study and its partners go to: http://nceph.anu.edu.au/Ausimmune/

Source: Australian National University Copywrite Australian National University