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Bite-Sized Brains Grown in a Lab Could Help Treat Fatal Diseases

·3 min read
Photo Illustration by Elizabeth Brockway/The Daily Beast/Getty
Photo Illustration by Elizabeth Brockway/The Daily Beast/Getty

It has all the makings of a Frankenstein-esque horror movie about science gone wrong: A group of scientists huddled over small organs vaguely resembling the human brain, tinkering with drugs and trying to keep them “alive” as long as possible.

But it’s not a freakshow science experiment. In fact, it’s about as far from a horror scene as you could get.

University of Cambridge scientists are growing miniature models of human brains in the lab in order to learn how to treat rare and fatal neurological diseases. In results published Thursday in Nature Neuroscience, the team argues it has hit on a breakthrough that could open the doorway to saving those afflicted by severe brain illnesses—and a whole host of other diseases, as well.

The new study focuses in particular on a confluence of two different disorders: the motor-neuron disease amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (or FTD). The two diseases often overlap as ALS/FTD—about a third of ALS patients develop FTD, often at around age 40–45. People who fall victim to ALS/FTD are hit with the worst effects of each disease: paralysis, muscle weakness, and a rapid decline in memory and cognitive function.

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There is no cure to either disease, one of which—ALS—is potentially fatal, and the combination of the two has proven obstinate to treatment. Screening for potential drugs for diseases like ALS/FTD is especially challenging when patients are suffering from a host of devastating symptoms.

But one workaround researchers have pioneered in recent years is the development of organoids: small models of human organs that act as a kind of laboratory proxy for the real thing. Researchers take a culture of skin cells, revert them to stem cells, and reprogram those stem cells to grow into the elements of a particular tissue or organ.

Those cells can even be modeled to emulate certain diseases or genetic disorders.

Organoids hardly look like the fully-grown organs they are supposed to model. But biologically, they can exhibit most of the same traits. Scientists have already used organoids to study things like liver damage, and respiratory infections in the lungs—including the behemoth of the century in COVID-19.

The trick is that organoids are hard to keep alive, since over time they eventually develop a dying core. This is especially true for brain organoids.

“The brain is probably our most complex organ,” study co-author András Lakatos, a neuroscientist at the University of Cambridge, told The Daily Beast. “It has the widest range of different types of cells that have yet to be fully explored.”

In this new study, however, the Cambridge team said it found a way to keep brain organoids alive for as long as 240 days—even ones that possess the mutations that lead to ALS/FTD. (In unpublished work, the team says it has been able to keep some organoids alive for 340 days.) The trick appears to be a new technique in slicing cell cultures that helps deliver more oxygen and nutrients to organoid parts.

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The research team grew one of these hardier mini-brains with the genetic mutations most commonly associated with ALS/FTD, and as the disease progressed, they learned which brain cells were afflicted earlier on (particularly astroglia, the neural cells which govern muscle movements and cognition). The team said it was able to affirm the efficacy of one known drug, GSK2606414, in relieving cell stress and death caused by ALS/FTD.

“Our findings hint that an early multi-target strategy may be required for a more optimal treatment strategy [for ALS/FTD],” said Lakatos.

With the ability to keep brain organoids alive longer, the hope is that other treatments for ALS/FTD—and other brain diseases—can be tested out much more rapidly in the near future. Whereas it once took decades to find an effective treatment for certain diseases, this research suggests that the timeline could soon shrink to just a few years.

Read more at The Daily Beast.

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