A scientist’s daughter was born with a rare disease, so he began to study it. An anonymous donor just chipped in $25 million.

Ben Prosser had devoted more than a decade of his scientific career to the problem of heart failure, contributing valuable new insights to a disease that affects millions. Then in August 2018, life handed him a rare medical puzzle he could not solve: his infant daughter, Lucy.

Several times a day, erratic signals were taking over the baby girl’s brain, causing her to twitch involuntarily and sometimes cry out in pain — a type of seizures called infantile spasms. Genetic testing revealed the cause: She’d been born with a rare mutation that meant she might never walk or talk.

What insight could he, a heart specialist at the University of Pennsylvania, possibly offer into a disorder of the brain?

More than four years later, the answer turns out to be: a lot. Within weeks of the diagnosis, Prosser joined forces with two prominent scientists next door, at Children’s Hospital of Philadelphia, and he started shifting the focus of his lab toward neurodevelopmental diseases like his daughter’s. In February, an anonymous donor gave them $25 million, potentially allowing the group to start testing treatments in children in as little as two years.

Prosser, an associate professor of physiology at Penn’s Perelman School of Medicine, is cautious about the chance of success. Yet the landscape for tackling rare diseases has changed dramatically in recent years — with the discovery of hundreds of new disease-causing mutations and the emergence of genetic therapies for putting that knowledge to work.

And Lucy’s rare disease, which occurs in 1 out of 30,000 children, would benefit from a rare stroke of good luck: Against all odds, her father was in a position to do something about it.

But first, he had to learn what was making her sick.

» READ MORE: Childhood epilepsies were once a medical mystery. Now, several kinds of treatments hold promise.

Lucy’s disorder was so rare that it didn’t have a proper name, just an alphabet soup designation: STXBP1 encephalopathy. Her father had never heard of it.

In an effort to make sense of his daughter’s complex condition, Prosser sought refuge the only way he knew how: by reading the scientific literature. Surely, plenty of researchers had to be studying it, and someone would be working on a promising therapy?

He found almost nothing. But on one of the few studies he found — published just two years before Lucy was born — Prosser saw that one of the authors was Ingo Helbig, a neurologist at CHOP.

Just two weeks later, Prosser was in a room with Helbig and colleague Beverly L. Davidson, an expert in the fast-moving field of gene therapy, mapping out strategy on a whiteboard.

“That’s Ben’s superpower,” said his wife, Erin, a marketing executive. “Bringing people together.”

They told him how the STXBP1 gene carried the recipe for the human body to make a crucial protein, enabling brain cells to communicate with one another. But the slightest glitch in that recipe could cause epileptic seizures and neurodevelopmental delays.

One such mutation was the equivalent of a one-letter typo. If you imagine the correct recipe as a sentence — say, “The cat ran down the street,” the mutated version became “The mat ran down the street.” In other children, the mutation was like a molecular stop sign, causing the brain to stop reading the recipe midway through: “The cat ran.”

In Lucy’s case, her father learned, the mutation prevented her brain cells from stitching together the pieces of the sentence into a finished product. The words were there — cat, ran, down, street — but they ended up on the cutting-room floor.

As the three scientists began to explore possible solutions, the seizures continued. Lucy was in and out of the hospital for months, as her doctors unsuccessfully tried one anti-epileptic medication, then another.

Her mom carefully logged each episode in a journal — the date, the time, how long it lasted — and took videos with her phone. They weren’t dramatic convulsions, but a rapid-fire series of small twitches called infantile spasms. The girl’s eyes would flick upward to the right, and her shoulders gave a quick shrug — perhaps 50 times in three minutes, with half a dozen such episodes a day.

“There’s nothing you can really do,” her mom said. “You just have to count, and hold her hand, and tell her it’s OK.”

In mid-November of 2018, the Prossers tried a new approach: an extreme version of the popular ketogenic diet.

When adults try various low-carbohydrate keto diets for weight loss, they typically aim to get two-thirds of their calories from fat. But in order to control Lucy’s seizures, nutritionists told the Prossers she would need to get 90% from fat. Avocados mashed up with mayonnaise. Greek yogurt mixed with grapeseed oil.

“Everything is measured out to a tenth of a gram,” Ben Prosser said.

Physicians do not fully understand why the diet can help some children with epilepsy, but by forcing brain cells to burn fat instead of carbohydrate sugars, it seems to remodel the metabolism in a way that calms a hyperactive brain, Prosser said.

The diet doesn’t work for everyone. But after a month and a half on the diet, on Dec. 29, Lucy went one full day without seizures. Then a second day, and a third.

Lucy has now been seizure-free for more than four years.

Whereas once Lucy seemed disengaged and unresponsive, she began to pay close attention to her surroundings, lighting up the room with a smile when she saw her parents or her big brother, Sam, who is two years older.

“I didn’t know if she was ever going to know that I’m her mom,” Erin Prosser said. “Now, she knows we’re her people.”

Yet the seizures had been just one symptom of Lucy’s underlying disorder. Her brain cells still could not communicate well with one another, meaning that she would have trouble with all the basic skills of life: learning, problem-solving, walking, and talking.

Prosser and the scientists at CHOP continued to work on a multipronged strategy, which they had sketched out that first day on the whiteboard.

The key was that in Lucy and other children with her disorder, the mutations occur in just one of their two copies of the STXBP1 gene. The other one is just fine — meaning their brains make half as much of the key protein as they needed.

One option was gene therapy — replacing the defective copy of the gene with a normal one. The first such treatment had been approved by the FDA just the year before, based on research at CHOP, for treating a rare form of blindness.

Another possibility was an emerging genetic technique called ASO, which they could use to maximize the output from her “good” recipe while leaving the other flawed one alone.

But the STXBP1 protein is hard to study. It is found only in the brain, so doctors can’t measure it with a simple blood test.

For that, Ben Prosser needed to make copies of his daughter’s brain cells in a lab.

Prosser took blood samples from Lucy and from his own arm and sent them off to a lab at CHOP. Scientists there reprogrammed their blood cells into blank slates: stem cells. These induced stem cells then were converted once again into brain cells — some of them exact copies of Lucy’s, and some of her father’s.

When he tested the copies of his own brain cells, Prosser found that they made normal levels of the key protein. Lucy’s made only half as much.

But then, using a gene-editing technique called CRISPR, Prosser was able to correct the flawed copy of Lucy’s gene. Her cells then were able to make enough protein.

With the results, and other pilot experiments in mice, Prosser and his partners started to win small grants. One came from a family of a patient with a similar disorder. Another came from the American Epilepsy Society, then the National Institutes of Health.

In February came the big one — $25 million, for a joint center at Penn and CHOP that will study Lucy’s condition and related disorders.

In a world where everyone affected by rare disease is striving for funds and attention, the parents of other children with these conditions can hardly believe their luck. Prosser is now on the scientific advisory board of a support group called the STXBP1 Foundation, which also contributed research funds. And against all odds, another scientist, Columbia University cell biologist Michael Boland, has a son with Lucy’s disorder, and he is now on the board, too.

Lucy sat on the floor of the Prossers’ living room one day in February, raising her arms in the air, expectantly.

“Do you want to go step-step?” her father asked.

Taking her hands in his, Prosser pulled her gently to her feet, and she managed a few stiff-legged steps before falling to the floor.

More than four years after the diagnosis, Lucy gets regular therapy, attends a specialized school, and is now on a less-extreme version of the keto diet. She can say “dada” and mouth the word “mama,” though no sound comes out. Developmentally, she is the equivalent of a 1-year-old.

As a parent, worried that every passing month represents a dwindling opportunity to make a difference in Lucy’s development, Prosser wishes he could give her some cutting-edge medication immediately. As a scientist, he is more cautious about predicting when he and his partners could develop a treatment, but he feels increasingly optimistic.

“I used to say five years,” he said. “It’s shorter than that now.”

Davidson, the gene-therapy specialist at CHOP, said it might be possible to test treatments in as little as two years. That could be gene therapy, ASO, or perhaps some existing drug that was designed for another purpose.

“We’re taking as many shots on goal as we can,” she said.

Among the many rooting for Lucy is big brother Sam, now age 6. On Jan. 1, he announced to the family that he had made his sister the subject of a special New Year’s wish.

“She’s going to walk, and talk, and know things,” he said.

With enough shots on goal, perhaps someday soon, she will.