in

Laboratory “mini brains” created for the treatment of neurodegenerative diseases

They were produced by researchers at the University of Cambridge in the UK. They will be used to study an intractable neurological disorder that causes paralysis and dementia, and for the first time they have been able to cultivate them for almost a year

Mb 1
So are the mini-brains that they developed at the University of Cambridge, from cells of patients with amyotrophic lateral sclerosis that overlaps with frontotemporal dementia (ALS / FTD) / Andras Lakatos / University of Cambridge

Researchers from the University of Cambridge in the UK managed to produce “mini brains” that allow the study of a deadly and intractable neurological disorder that causes paralysis and dementia. For the first time, they have been able to cultivate them for almost a year. It implies an advance in the search for treatments for a common form of motor neuron disease, amyotrophic lateral sclerosis, it often overlaps with frontotemporal dementia (known by the initials ALS / FTD).

The disease can affect younger people because it occurs mainly after 40-45 years. These conditions cause devastating symptoms of muscle weakness with changes in memory, behavior, and personality.

The development of tiny organ-like models of the brain – called organoids – enables researchers to understand what happens in the early stages of the disease, long before symptoms begin to appear, and to detect potential drugs that are effective.

In general, organoids, often referred to as “mini organs,” are increasingly used to model human biology and disease. Only at the University of Cambridge are researchers using them to repair damaged livers, study SARS-CoV-2 lung infection, and model early pregnancy, among many other areas of research.

Mb 2
Organoids, Often Referred To As “Mini Organs,” Are Increasingly Being Used To Model Biology And Disease / University Of Washington / Archive

Typically, researchers take cells from a patient’s skin and reprogram them to their stem cell stage, a very early time of development, when they still have the potential to become most cell types. These can then be grown as 3D groups that mimic particular elements of an organ. As many diseases are caused in part by defects in DNA, this technique allows researchers to see how cellular changes, often associated with these genetic mutations, lead to disease.

Scientists at the John van Geest Center for Brain Repair at the University of Cambridge published their research in the journal Nature Neuroscience, where they detailed that used stem cells derived from ALS / FTD patients to grow brain organoids that are about the size of a pea. These resemble parts of the human cerebral cortex in terms of their embryonic and fetal developmental milestones, 3D architecture, diversity of cell types, and cell-cell interactions.

Although this is not the first time that scientists have grown mini brains from patients with neurodegenerative diseases, most efforts have only been able to grow them for a relatively short period of time, representing a limited spectrum of dementia-related disorders.

Mb 3
The Researchers Managed To Grow The Mini-Brains For 240 Days From Stem Cells That Harbor The Most Common Genetic Mutation In Als / Ftd. In Another Unpublished Work, He Has Cultivated Them For 340 Days.

In the findings published in Nature Neuroscience, the Cambridge team reports that these models were grown for 240 days from stem cells harboring the most common gene mutation in ALS / FTD, which was not previously possible, and in unpublished work, the team reports that they have cultivated for 340 days.

András Lakatos, lead author who led the research at the Cambridge Department of Clinical Neurosciences, pointed out that: “Neurodegenerative diseases are very complex disorders that can affect many different cell types and interact at different times as the cells progress. diseases. To get closer to capturing this complexity, we need models that are longer-lived and replicate the composition of those populations of human brain cells in which disturbances often occur, and this is what our approach offers. Not only can we see what can happen early in the disease, long before a patient experiences any symptoms, but we can also begin to see how the alterations change over time in each cell.”

Although organoids are generally grown as balls of cells, the paper’s first author, Kornélia Szebényi, generated organoid section cultures derived from patient cells in Dr. Lakatos’ laboratory. This technique ensured that most of the cells within the model could receive the necessary nutrients to keep them alive.

Szebényi reported that “when cells are grouped into larger spheres, those in the nucleus may not receive sufficient nutrition, which may explain why previous attempts to grow long-term organoids from patients’ cells have been difficult.”

Mb 4
While Organoids Are Generally Grown As Cell Balls, This Time It Was Done With Organoid Section Cultures Derived From Patient Cells / Archive

Using this approach, Szebényi and his colleagues observed changes that occur in organoid cells at a very early stage, including cellular stress, DNA damage, and changes in the way DNA is transcribed into proteins. These changes affected nerve and other brain cells known as astroglia, which orchestrate muscle movements and mental abilities.

“Although these initial alterations were subtle, we were surprised by how the first changes occurred in our human ALS / FTD model,” Lakatos added. This and other recent studies suggest that damage can begin to accumulate as soon as we are born. We will need more research to understand if this is really the case, or if this process is advanced in organoids by artificial conditions”.

In addition to being useful to understand the development of the disease, organoids can be a powerful tool to screen for potential medications and see which ones can prevent or slow disease progression. This is a crucial advantage of organoids, as animal models often do not show the typical disease-relevant changes., and it would not be feasible to sample the human brain for this research.

The team showed that a drug, GSK2606414, was effective in alleviating common cellular problems in ALS / FTD, including toxic protein buildup, cellular stress, and nerve cell loss, thereby blocking one of the pathways that contribute to the disease. Similar drugs that are more suitable are now being tested in clinical trials for neurodegenerative diseases.

Mb 5
When Developing Organoids, They Seek To Find Targets To Develop Future Therapies (Getty Images)

Gabriel Balmus of the UK Dementia Research Institute at the University of Cambridge, contributing author of the paper: “By modeling some of the mechanisms that lead to DNA damage in nerve cells and showing how these can lead to various cellular dysfunctions, we may also be able to identify other possible drug targets”.

“Currently we do not have very effective options to treat ALS / FTD – added Lakatos – and while there is much more work to do our discovery at least offers hope that over time it will be possible to prevent or slow down the disease process. It is also possible in the future to be able to take cells from a patient’s skin, reprogram them to grow their ‘mini brain’ and test what unique combination of drugs is best suited to their disease,” he concluded.

Comments

Leave a Reply

Your email address will not be published. Required fields are marked *

GIPHY App Key not set. Please check settings

    Written by Christina d'souza

    Proofreader, editor, journalist. I have been doing my favourite thing for more than six years.

    Doc 1

    Cases on the rise, deaths and bed occupancy on the decline: what the experts say about the numbers of the pandemic

    The Witcher 1

    The Witcher 2: they release the surprise trailer, with Henry Cavill