November 21, 2018

Could lab-grown human minibrains help treat Alzheimer’s and epilepsy?

This year, as the worlds of science, technology and literature marked the bicentenary of Mary Shelley’s Frankenstein, in some laboratories human cells were being coaxed into a tiny version of the organ that most defines us.

Depending on where you sit, these “minibrains” – formally known as cerebral organoids – could rival Shelley’s creation on the monstrosity scale, raising deep moral questions about consciousness and the nature of humanity.

But they also promise hope of a cure for illnesses ranging from childhood epilepsy to Alzheimer’s disease and brain cancer.

I’ve come to Melbourne’s Florey Institute of Neuroscience and Mental Health to hunt a minibrain down. I’m expecting to find it in a dish, on a bench or perhaps in a fridge.

As it happens, the first one we stumble upon is in the bin.

A special bin for biowaste, of course. The neural tissue has died after serving its purpose and is now merely a smudge of pink on a plastic slide.

Still, it seems inconceivable that this miracle of science could qualify as rubbish.

Steve Petrou

Prof Steve Petrou in the lab. Credit – Pat Scala

The contrast becomes more extreme when I sit down to chat with Florey Institute director Professor Steven Petrou. He is leading research that creates organoids to mimic the behaviour of the brains of children with rare, debilitating forms of epilepsy.

“Some of these kids can’t speak, are not mobile, they sit in a cot, they have 20 seizures a day and they die when they’re 12. So, absolutely devastating neuro-developmental disorders,”The researchers take skin cells from the children, turn them into pluripotent stem cells that can form almost any tissue in the body, then direct them to become neurons.

Through a microscope you can clearly see the slender bodies of those brain cells afloat in a watery matrix. Hook them up to electrodes and you get something mind-bending. These guys are talking to each other – the computer shows spikes of electrical activity as the neurons fire.

A multi-electrode array used to measure electrical activity in minibrains

But for the kids Petrou is trying to help, the chatter is out of whack. Some have a mutation in a gene called SCN2A that controls the passage of sodium in and out of the neuron.

“This is a gain of function of excitation, so this channel works too hard and produces epilepsy,” says Petrou.

Replicating that glitch in a dish has allowed the researchers to tailor a treatment right there on the bench; Petrou is on the verge of announcing a clinical trial of a gene therapy to treat one variant of the disorder.

And it won’t just aim to stop the seizures.

The idea with precision medicine in this application is if you can fix the fundamental disorder far enough back in the pathological chain, you should fix all the problems,” says Petrou.
If the treatment works, these kids could be spared the intellectual disability and movement disorders that go hand-in-glove with constant seizures.

Complexity is something of a buzzword in organoid research. Recent Australian research upped the stakes by 3D-printing brain tissue, bringing a replica brain on a bench into tantalising – if very distant – focus.

But Petrou stresses just how tricky that task is going to be.

“We know how fragile a real brain is. One genetic mutation, some trauma, and that brain doesn’t work anymore,” he says. “It is so easy to break and therefore that means it is probably going to be so difficult to reproduce.”

Nonetheless, as the technology advances you wonder if those organoids could grow to the point where one day they start to gain bona fide moral status.

If that happens, the first sign might just be a very slight pang as scientists toss their dreaming minibrains into the garbage.

This is an edited extract from a larger story by Paul Biegler which appeared in the Sydney Morning Herald

Article sourced from The Florey Institute

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