Multiple System Atrophy: Groundbreaking NZ-led study prompts rethink about devastating disorder

A study led by the University of Auckland’s Dr Birger Victor Dieriks has uncovered some crucial new research avenues for scientists to explore in the battle against devastating neurodegenerative disorder Multiple System Atrophy (MSA). Photo / University of Auckland

• Multiple System Atrophy can quickly reduce an active, healthy person to a state of near-total immobility, with life expectancy just five to 10 years.
• Now, a New Zealand-led study has challenged long-held beliefs about the root causes of the devastating neurodegenerative disorder.
• The just-published findings also open up potential new avenues for therapy for the disorder, which remains without a cure.

Groundbreaking Kiwi-led research is prompting a rethink about what causes a rare but devastating neurodegenerative disorder – and may prove a turning point for new therapies.

Afflicting an estimated four in 100,000 people, Multiple System Atrophy (MSA) causes gradual damage to nerve cells in the brain, affecting movement, balance and basic functions like breathing, speech, digestion and bladder control.

Often misdiagnosed as Parkinson’s, it’s so aggressive that it can quickly reduce a vibrant, active person to a state of near-total immobility – life expectancy for those diagnosed is typically just five to 10 years - and there remains no cure.

But a new study, led by the University of Auckland’s Dr Birger Victor Dieriks, has uncovered some crucial new avenues for scientists to explore.

For decades, scientists have believed MSA’s primary culprits are cells called oligodendrocytes, which produce a protective sheath around nerve fibres.

In MSA patients, these cells are known to accumulate clumps of a specific protein called alpha synuclein – yet it wasn’t clear how this related to the rapid and widespread killing of neurons observed in patients.

Dieriks’ team, including PhD student James Wiseman and University of Sydney neuroscientist Professor Glenda Halliday, now believe they’ve uncovered the real driver of that neurodegeneration, which appears to lie within the neurons themselves.

That discovery was critical, as it suggested that therapies targeting alpha synuclein in oligodendrocytes might not be effective in halting the disease’s progression.

Using cutting-edge super-resolution microscopy and advanced alpha synucleinantibodies, the researchers discovered that toxic protein clumps penetrate the nuclei of neurons in MSA patients.

Once inside, they disrupt the 3D organisation of the nucleus, leading to its destruction and, ultimately, the death of the neuron.

“This finding breaks with established dogma,” said Dieriks, a senior research fellow at the university’s Centre for Brain Research.

“For years, the focus has been on the oligodendrocytes, because that’s where most of the alpha synuclein clumps were found.

“But our research shows the real killer is the impact of alpha synuclein aggregates on neurons - and this explains why MSA progresses so much faster than similar diseases, such as Parkinson’s.”

The findings were viewed as more than just a scientific breakthrough, but a potential turning point in the fight against MSA.

It meant researchers could now focus on developing treatments that specifically targeted aggregates in neurons, paving the way for new therapies.

“With each new discovery, the hope grows that one day, MSA will no longer be a life sentence but a condition that can be managed - or even cured,” Dieriks said.

Jamie Morton is a specialist in science and environmental reporting. He joined the Herald in 2011 and writes about everything from conservation and climate change to natural hazards and new technology.

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