Scientists found a way to restore brain cells impaired by a rare genetic disorder

JUANA SUMMERS, HOST:

Scientists have found a way to restore brain cells impaired by a rare genetic disorder called Timothy syndrome. NPR's Jon Hamilton reports the method offers hope for treating a wide range of other conditions, including epilepsy and autism spectrum disorder.

JON HAMILTON, BYLINE: Timothy syndrome affects only a few dozen people worldwide. But Dr. Sergiu Pasca of Stanford University says learning how to treat the disorder might help millions of people.

SERGIU PASCA: Rare syndromes that are very clearly defined genetically are sort of like windows, or almost like Rosetta Stones into understanding other more common conditions.

HAMILTON: Like schizophrenia, autism and epilepsy - those conditions often run in families, but they involve changes to many different genes, which makes them hard to study. So Pasca has spent the past 15 years focusing on an extremely rare condition with a very clear genetic origin.

PASCA: Timothy syndrome is caused by a single letter change in the genome. And this simple mutation causes a very severe neurodevelopmental disorder. These patients have autism. They have epilepsy. They have developmental delay. They have intellectual disability.

HAMILTON: They also have heart problems. To understand how a change in a single gene can do all this, Pasca and his team have been studying brain organoids, clusters of living human brain cells grown in the lab. The cells carry the same gene mutation found in people with Timothy syndrome. Pasca says that's allowed his team to see how the mutation leads to a range of abnormalities, including neurons that are small and less able to form connections.

PASCA: We've essentially catalog all these abnormalities. And at one point, we just gathered enough information about the disease that a therapeutic approach just kind of, like, revealed itself. It just became self-evident.

HAMILTON: The approach involves something called an antisense drug. In this case, the drug uses small pieces of genetic material that can enter a brain cell and, in effect, counteract the mutation responsible for Timothy syndrome. To see if the drug worked, Pasca's team transplanted clusters of mutated human cells into the brains of baby rats.

PASCA: And then after about 250 days or so of growing this tissue into the rat brain, we injected this therapeutic into the rat, inside the nervous system.

HAMILTON: Pasca says the bits of genetic material did just what they were supposed to.

PASCA: They go inside the cell. They do their job. And within a couple of days, you start rescuing or restoring all those defects that we've observed over the years.

HAMILTON: For example, the neurons got larger and formed more connections. The result, which appears in the journal Nature, sets the stage for testing the drug in people with Timothy syndrome. The finding also hints at a strategy for treating people with other genetic conditions that affect brain development. Pasca says these might include schizophrenia and autism. But Dr. Huda Zoghbi of Baylor College of Medicine says that's probably a ways off.

HUDA ZOGHBI: In psychiatric diseases, it's usually a much milder mutation. It's a mutation that you and I might have.

HAMILTON: Or several different mutations that interact with our life experiences. So for now, Zoghbi says, antisense drugs are probably best for genetic disorders that are simpler and better understood. She knows that the FDA has already approved an antisense drug for a rare condition called spinal muscular atrophy. And scientists are working on a drug for a neurodevelopmental condition called Angelman syndrome.

ZOGHBI: It's the beginning really of a new era, where many of these diseases that we first thought are untreatable, now we're learning they are actually treatable.

HAMILTON: Thanks, largely, to studies that show precisely how certain genetic changes affect the brain and nervous system. Jon Hamilton, NPR News.

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