Organoids are tiny versions of important human organs like heart and brain, roughly the size of a rice grain. They’re grown in the lab from stem cells (obtained from adult human beings) without the need to go experimenting on live human embryos.

What are they good for? Testing the effects of drugs, viruses… anything you like really. But ethically.

Having just published a post about organoids (Why grow tiny hearts? 11 June 2024), where I conjectured something about mini-brains, this piece from the American Association for the Advancement of Science (AAAS) couldn’t help but catch my eye…

When the COVID-19 pandemic erupted in early 2020, it hit certain populations much harder than others. Older adults, people with heart and lung disease, and people with conditions that compromise the immune system are all more likely to contract the SARS-CoV-2 virus—and tend to get much sicker when they do. Scientists have also realized that, among groups at higher risk of dying from COVID-19, people with Down syndrome are some of the most vulnerable.
Because individuals with this disorder have an extra copy of chromosome 21, they receive a double dose of certain genes, which can impact heart development, weaken the immune system, and cause mouth and throat abnormalities that make respiratory infections especially dangerous. COVID-19 also appears to be unusually severe in their brains. But while neurological problems are quite noticeable in other Long Covid patients, they are harder to quantify in people with Down syndrome, who already exhibit a variety of cognitive issues and have an increased risk of early-onset dementia.
It’s not ethical—or practical—to infect living human brains with SARS-CoV-2. So, to find out how the virus affects the brains of people with Down syndrome, scientists grew their own miniature ones. Using existing Down syndrome stem cell lines, the scientists [Dr Shaker and his team] crafted first-of-their-kind brain organoids: small, synthetic organ replicas that can be used to study disease in a lab setting. After growing these models, the team encased them with layers of specialized cells that mimic the structure and function of the choroid plexus—a structure that plays a critical role in maintaining the blood-brain barrier and protecting the brain from viruses.
Experiments revealed that, in people born with Down syndrome, the tight connections that ordinarily hold the choroid plexus cells together are disrupted. As a result, SARS-Cov-2 can more easily infiltrate the central nervous system, where it proceeds to wreak havoc on neurons, the team reports in Science Advances. “The barrier function of the choroid plexus prevents coronavirus from infecting brain cells, and this barrier is compromised in people with Down syndrome,” study author Ernst Wolvetang explains in a statement. “A crucial line of defense is missing.”
The researchers also used their organoids to test drugs that could potentially help compensate for these defects. They identified a number of promising therapies, including some already approved by the U.S. Food and Drug Administration to treat COVID-19 and other conditions. “The risk of hospitalization and death from coronavirus is much higher for people with Down syndrome, but until now there has been no clear data that explains why,” study author Mohammed Shaker says. “Thankfully, our lab-grown organoids allow us to unlock this information and find ways to address the problem.”

I quote the piece at length (with due acknowledgement to the AAAS!) because I don’t know how to link to an email inside a web-page (like the post you’re reading).

To those who’ve read my previous post on organoids, it’s all pretty clear, except for that anatomical term: choroid plexus. If you’re like me, not knowing my choroid plexus from my solar plexus, let’s just say it’s responsible for making spinal fluid. That’s the juice that bathes and protects the brain and spine. Plus keeping them nice and healthy. It’s an important ally of the blood-brain barrier.

In case you didn’t know, brain and spine aren’t plumbed directly into the blood supply: neat blood is too strong for them. What happens if blood gets into the brain? I can tell you: I spent weeks in hospital in 1962 because of that.

Oh, another important bit of jargon (if you follow the link to the original paper): SARS-CoV-2. That’s the proper name of the virus that causes the disease COVID-19.

The moral to this story is: Down’s syndrome sufferers often have a below-par choroid plexus, which lets SARS-CoV-2 get past the blood-brain barrier more easily, and so into the brain and kill the patient. Dr Shaker and his team have grown mini-brains to prove this, plus looking for medicines which help.

Isn’t Science wonderful.