Enhancing levels of 'healthy fats' like omega-3s in the brain could be beneficial in motor neurone disease (MND) finds a new study in fruit flies and brain cells, led by UCL researchers.
Previous epidemiological studies have linked high dietary levels of omega-3 fatty acids - like those found in oily fish, nuts and seeds - with a lower risk of developing MND, and longer survival in people affected by the disease. But until now, it was not well understood why this occurs.
A new study, published in Nature Neuroscience and led by researchers at the UK Dementia Research Institute (UK DRI) at UCL, and the UCL Institute of Healthy Ageing, found that increasing the levels of these healthy fats in the brain cells of fruit flies carrying a gene mutation called C9orf72, saw a 'dramatic' increase in their survival.
The C9orf72 mutation is the most common genetic cause of MND and a rare form of dementia, known as frontotemporal dementia (FTD). Cells were also collected from people with these conditions and converted into brain cells in the lab. Healthy fats also increased the survival of these MND/FTD brain cells.
The researchers believe that the findings unlock a new understanding of the mechanisms underlying MND and FTD.
Study leader Professor Adrian Isaacs (UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL) said: "Epidemiological studies suggest that people with a high intake of omega-3 fatty acids have a lower risk of developing motor neuron disease. Our study adds a deeper understanding of the mechanisms behind this.
"From our findings we can conclude that enhancing levels of omega-3 fatty acids in the brain may be beneficial in motor neuron disease. Of course, the next step is to test this in people. We first need to work out which specific fatty acid would be best to test in humans, and how we can deliver sufficient quantities to the brain. Then, we want to take these findings forward into a clinical trial."
MND, including its most common subtype amyotrophic lateral sclerosis (ALS), causes progressive muscle weakness due to the degeneration of motor neurons in the brain and spinal cord. It is estimated to affect 1 in 300 people in their lifetime, and there are currently no disease-modifying drugs available to treat the condition.
In the new study, researchers measured levels of different types of fats in human brain cells and in flies carrying the C9orf72 gene mutation. They found that the levels of poly-unsaturated fatty acids, including omega-3 fatty acids, were significantly reduced in the MND/FTD flies compared with a control. These fatty acids were also reduced in brain cells from people with MND/FTD.
There are two essential fatty acids that must be consumed in food, as the human body cannot produce them. They are alpha linoleic acid, a type of omega-3 fatty acid found in flaxseed, soybean and vegetable oils such as canola oil, and linoleic acid, a type of omega-6 fatty acid, found in similar foods.
The scientists first fed the flies linoleic acid and alpha linoleic acid, to test whether this would impact on their survival. They found that the amount of fatty acids in their diet led to a small improvement in the survival of the flies.
Next, they delivered the fatty acids directly to the brain cells of the flies by expressing the genes capable of producing them. They found that this increased the survival of the flies by 83%, from 15 days to 27.5 days.
They repeated the experiment in cells taken from people with MND/FTD and found that increasing levels of the fatty acids in the cells prolonged survival by 30%.
Professor Martin Giera, Head of Metabolomics Group at Leiden University Medical Center (LUMC), said: "Our study highlights the crucial role of lipids and their precisely regulated composition in health and disease. Importantly, our findings reveal that addressing these issues is not merely about providing the right components but involves carefully modulating endogenous lipid levels in specific locations.
"In summary, we establish a foundation for developing potential future therapies that leverage lipid metabolism - a concept with far-reaching implications beyond ALS, extending to a range of neurodegenerative diseases."
The study was funded by Alzheimer's Research UK and the UK DRI.
Dr Julia Dudley, Head of Research at Alzheimer's Research UK said: "With nearly one million people living with dementia in the UK, there is an urgent need to understand and treat the diseases that cause this condition, including rarer forms. Neurodegenerative diseases are complex, however some share similar genetic changes. This means that understanding how these changes affect the brain could ultimately lead to new treatment approaches for dementia.
"It is exciting to see findings which suggest that increasing levels of fatty acids, including omega-3 could be protective against motor neuron disease and frontotemporal dementia.
"At Alzheimer's Research UK, we are proud to support research that helps to broaden our understanding of rare forms of dementia and foster collaborations in dementia research across the UK. We are excited to see the next steps for this research which we hope will play a key role in bringing us closer to a cure."
