Lab-grown ‘mini brains’ to pave way for dementia treatment

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London– UK researchers have developed ‘mini brains’ that allow them to study a fatal and untreatable neurological disorder causing paralysis and dementia.

This is not the first time scientists have grown mini brains from patients with neurodegenerative diseases, but most efforts have only been able to grow them for a relatively short time frame.

For the first time, scientists at the University of Cambridge were able to grow these small organ-like models (organoids) of the brain for almost a year.

A common form of motor neurone disease, amyotrophic lateral sclerosis, often overlaps with frontotemporal dementia (ALS/FTD) and can affect younger people, occurring mostly after the age of 40-45. These conditions cause devastating symptoms of muscle weakness with changes in memory, behaviour, and personality.

In findings, published in the journal Nature Neuroscience, the Cambridge team reported growing these models for 240 days from stem cells harbouring the commonest genetic mutation in ALS/FTD, which was not previously possible — and in unpublished work, the team has grown them for 340 days.

“Neurodegenerative diseases are very complex disorders that can affect many different cell types and how these cells interact at different times as the diseases progress,” said Dr Andras Lakatos, from the Cambridge’s Department of Clinical Neurosciences.

“To come close to capturing this complexity, we need models that are more long-lived and replicate the composition of those human brain cell populations in which disturbances typically occur, and this is what our approach offers. Not only can we see what may happen early on in the disease — long before a patient might experience any symptoms — but we can also begin to see how the disturbances change over time in each cell,” Lakatos added.

While organoids are usually grown as balls of cells, the team generated patient cell-derived organoid slice cultures in laboratory. This technique ensured that most cells within the model could receive the nutrients required to keep them alive.

Using this approach, the team observed changes occurring in the cells of the organoids at a very early stage, including cell stress, damage to DNA, and changes in how the DNA is transcribed into proteins. These changes affected those nerve cells and other brain cells known as astroglia, which orchestrate muscle movements and mental abilities.

Besides understanding disease development, organoids can also be a powerful tool for screening potential drugs.

The team showed that drug GSK2606414 was effective at relieving common cellular problems in ALS/FTD, including the accumulation of toxic proteins, cell stress and the loss of nerve cells, hence blocking one of the pathways that contributes to disease. (IANS)


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