MS Australia is ramping up research to find out more about the neurological disease to combat the sharp surge in prevalence.
Kathy Skantzos reports
The prevalence of multiple sclerosis (MS) has increased in every world region from 2013 to 2020, with a person diagnosed every five minutes, according to MS Australia CEO Rohan Greenland.
The latest data from MS Australia and the University of Tasmania’s Menzies Institute for Medical Research shows that the neurological disease, affecting mostly young to middle-aged women, rose in Australia by 30% over four years, from 25,607 in 2017 to 33,335 in 2021.
The data, published in Health Economic Impact of Multiple Sclerosis in Australia in 2021, shows the number of people living with MS more than doubled from 2010 to 2017, with an increase of 4,324 people. Consequently, the prevalence of MS in Australia has risen considerably. There were 131 people living with MS per 100,000 people in Australia in 2021, up from 103.7 per 100,000 people in 2017.
MS Australia has funded 22 new MS-focused projects this year, injecting over $3 million to address the sharp rise in cases, including studies that examine family genetics, the impact of diet on brain health, and cellular repair and regeneration.
“MS is extraordinarily complex, and we need to cover much ground to advance our understanding of the disease and to devise better approaches to combat it,” Mr Greenland said.
“We’ll be hitting MS from every direction with these research projects to ensure we go further and faster towards better treatments and prevention of the disease.”
Commonly adult onset, diagnosed usually between the ages of 20 and 40 and mostly in women, MS is the neurodegenerative disease identified by demyelinating lesions in the brain and spinal cord. High inflammation is thought to cause the death the myelinating cells, oligodendrocytes.
Symptoms include visual impairment, sensory disturbances, cognitive problems, sexual dysfunction, motor dysfunction and weakness, bowel or bladder continence, fatigue, sleep disturbance, anxiety and depression, and can result in marked declines in both physical and psychosocial health-related quality of life.
Lifestyle factors, such as smoking, low sun exposure and consequently low vitamin D levels, and being overweight increase the risk of developing MS. New research from Curtin University and Deakin’s Institute for Physical Activity and Nutrition (IPAN) is showing the link between diet and MS.
Complex risk factors
One of the interim report authors, Professor Bruce Taylor, principal research fellow at the Menzies Institute for Medical Research and clinical neurologist at the Royal Hobart Hospital, said the rise in MS incidence and prevalence over the past decade was concerning.
“MS is a rapidly progressive neurodegenerative disease which results in an accumulation of disability. People think of MS as a disease of young women but that’s when it starts and once you’ve got MS you’ve got it for life,” he told Medical Forum.
As well as genetics, he said there were several epigenetic factors that played a role in developing MS.
Research has shown that the risk of MS is significantly increased if someone has had early adolescent obesity, which is also on the rise.
“If we could reduce adolescent obesity, we could potentially reduce 50% of cases of MS,” Prof Taylor said. “And the incidence of MS is higher in Tasmania compared to northern Queensland due to the role sun exposure plays in getting sufficient vitamin D.
“We think people aren’t getting as much sun – since the 1980s ‘slip, slop, slap’ message – and we know less sun exposure reduces vitamin D in your system which has a direct impact on the immune system.”
Being female increases the likelihood of MS by three times compared with men, and women who put off pregnancy until their later reproductive years increase their risk due to pregnancy’s immunology protective factors.
“Every pregnancy reduces the risk of developing MS by 50%, and women are having less children and later,” he said.
Then exposure to the Epstein-Barr Virus (EBV), which includes 90% of the population, is clearly linked to MS.
“It’s the obligatory risk factor for getting MS,” Prof Taylor said. “We’ve known this link between EBV and MS for many years. The risk of having MS without EBV approaches zero, and with the virus it’s 99.99% so it is a major risk factor.
“If a vaccine for EBV were developed, it could significantly reduce the numbers of MS.”
He said that genetic makeup and genomic host-pathogen interaction added complexity to risk factors for the disease and how these risk factors interacted was also complicated.
“We know smoking interacts with genetics, EBV exposure interacts with genes as does obesity,” Prof Taylor said.
Role of diet
Research at IPAN and Curtin University is investigating the largely unknown role of diet – including ultra-processed foods, fish and dairy products – in the onset of MS.
Professor Lucinda Black, who is leading the MS Australia-funded research through the MS Nutrition Research Team, started looking into diet and MS in 2016 at Curtin University with a fellowship from MSWA.
Previous research led by Prof Black showed a healthy Mediterranean-style diet – including chicken, fish, eggs, vegetables, legumes, and some unprocessed red meat – was associated with reduced likelihood of the first clinical diagnosis of demyelination in the brain and spinal cord (FCD), while ultra-processed foods and a pro-inflammatory diet were associated with higher likelihood of FCD.
There was a lot of confusion about diet and MS, and many different diets were marketed to people with the disease that might restrict certain food groups or foods that could help their symptoms.
“There isn’t enough high-quality, conclusive evidence to support any of the special diets for people with MS,” Prof Black said. “We’re aiming to generate high-quality evidence about the link between diet and risk of MS, whether diet can help prevent MS, and for those with MS what is the best diet for their condition.”
“What we’ve found so far, using data from Australia, is that a healthy diet overall is linked to a lower likelihood of getting MS, and we’ve seen that same pattern in the American study,” she said.
The Australian data shows that consuming a moderate amount of unprocessed red meat and oily fish in accordance with the Australian Dietary Guidelines (ADG) is linked to a lower risk of getting MS, and higher consumption of ultra-processed foods increases the likelihood of MS.
“Most Australians don’t eat enough fruit or vegetables, young adult women generally don’t eat enough unprocessed red meat, we all probably don’t eat enough oily fish, so it’s about following the ADG and not necessarily going on a restricted diet.”
Prof Black’s team is also developing an online nutrition education program tailored for, and co-designed with, individuals with MS.
“We’re talking to people with MS about their attitudes and behaviours around diet and getting their input in all our research projects. What they’ve asked for is education around diet that’s relevant to them, not necessarily information that’s relevant to the general population.”
However, Prof Black said diet was only part of a bigger picture alongside research into physical activity, stress, sleep, mental health, vitamin D status, and other environmental risk factors.
Dr Eleonor Dunlop, from the Curtin School of Population Health, is an MS Australia Postdoctoral Fellow and Accredited Practising Dietitian working alongside Prof Black. She is looking at the role of diet in children with MS, which is rare but the incidence in increasing.
The research, which draws on a study conducted in Canada led by Professor Helen Tremlett at the University of British Columbia, could lead to the creation of evidence-based dietary advice for children at high risk of developing MS.
Muscle weakness
Meanwhile, MS Australia is also funding research at Edith Cowan University that aims to understand how motor neuron behaviour contributes to muscle weakness.
The research is led by Dr Christopher Latella, from ECU’s School of Medical and Health Sciences, and builds on evidence suggesting a problem with serotonin and noradrenaline in the nervous system of people with MS.
However, it is not yet known if the spinal motor neurons are also affected. The research is looking into the motor neuron firing of persistent inward currents and will record the electrical activity of leg muscles to determine the firing of nerve cells during voluntary muscle contractions.
“There’s been some evidence to suggest that certain centres in the brain might become dysfunctional and those centres in particular are responsible for the release of specific neurotransmitters such as serotonin and noradrenaline, Dr Latella said.
“Those centres of the brain also have important interruptions with the spinal cord, in particular nerves that control muscles.”
He will investigate whether changes in the properties of the motor neurons influence performance of tasks like walking and standing in people living with MS.
“Both serotonin and noradrenaline are important for this system to work properly, so if both are disrupted in MS, it might be one of the contributors to muscle weakness and fatigue, and we know that’s quite prevalent in people with MS.”
Cure and treatment
Research led by Associate Professor Jennifer Rodger from UWA and the Perron Institute will use repetitive transcranial magnetic stimulation (rTMS) to generate small electrical pulses in the brain to explore if this can improve the survival of the myelin-producing oligodendrocytes.
The project could open the door for treatments that maximise the survival of oligodendrocytes.
From the University of Sydney, Associate Professor Laura Piccio is studying the role of TREM2 proteins, located on microglia in the phagocytosis of myelin debris, and remyelination. Preliminary results suggest the activation of TREM2 could enhance myelin debris clearance and remyelination.
While Prof Taylor said a cure is likely to be far off, MS Australia’s funding towards the new studies is taking steps to find better treatments, preventions, and understand the disease affecting 2.5 million people worldwide.
“At this stage a cure looks difficult,” Prof Taylor said, “though our treatments have made a huge difference for the prognosis of people with MS.
While newer treatments have made a difference, prognosis is still serious for primary progressive MS (PPMS), affecting 10-15% of people with MS, where there is a gradual worsening of neurologic symptoms and an accumulation of disability.
“We hope that in the next 10 years we will have an effective treatment for progressive MS, and if we had that we will be able to turn it into a much more benign disease,” Prof Taylor said.