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Researchers Hope Experimental Gene Therapy Is An Answer To A Fatal Genetic Disorder

ARI SHAPIRO, HOST:

Now the story of a fatal genetic disease, a tenacious scientist and a family that never lost hope. Conner Curran was 4 when he was diagnosed with Duchenne muscular dystrophy. His muscles were already beginning to waste away. A doctor offered Conner's parents some advice.

JESSICA CURRAN: Take your son home. Love him. Take him on trips while he's walking. Give him a good life and enjoy him because there's really not many options right now.

SHAPIRO: Today, Conner is 9 and not just walking, but running. The reason - an experimental gene therapy. Here's NPR's Jon Hamilton.

JON HAMILTON, BYLINE: Conner's parents, Jessica and Christopher Curran, refused to accept that doctor's grim prognosis. But by the time Conner got to first grade, Jessica could see that her son was struggling.

CURRAN: He pulled himself up the stairs. He would make it past four stairs, and he couldn't do the rest. He could not last a full day in school. The teacher would say, we let him take a little nap in the classroom. I'm thinking, what?

HAMILTON: The Currans knew that scientists were working on a treatment.

CURRAN: I'd say about a year after Conner's diagnosis, we did hear the words gene therapy.

HAMILTON: Gene therapy seemed like the answer. After all, children with Duchenne muscular dystrophy lack a functional version of a gene called dystrophin, which helps muscles stay healthy.

JUDE SAMULSKI: The concept is very simple. You're missing a gene, so you're putting it back.

HAMILTON: That's Jude Samulski from the University of North Carolina. He's spent his career working to make gene therapy a reality. It all began in 1984 when Samulski was a graduate student at the University of Florida. He was part of a team that cloned a virus called AAV. AAV is unusual because it infects people without making them sick. Samulski saw the virus as a safe way to transport healthy genes to ailing muscle cells.

SAMULSKI: It's a molecular FedEx truck. It carries a genetic payload, and it's delivering it to its target.

HAMILTON: But delivering a gene is harder than delivering a package. And the dystrophin gene was especially challenging. For one thing, it has too much genetic information to cram inside a virus so tiny you need an electron microscope just to see it. Samulski says progress came one small step at a time.

SAMULSKI: This was very challenging. It was the Mount Everest of the gene therapy community. And each one of these steps was like setting up base camp.

HAMILTON: Then in 1999, Samulski's base camp got hit by an avalanche. A teenager named Jesse Gelsinger died in a gene therapy experiment. The experiment didn't involve muscular dystrophy or the AAV virus, but Samulski says those details didn't matter.

SAMULSKI: It stopped everything.

HAMILTON: Gene therapy trials were postponed or abandoned. Investors disappeared. So did research funding. But Samulski says one group never wavered - the Muscular Dystrophy Association.

SAMULSKI: If the MDA didn't step in, the field was going to dry up and die.

HAMILTON: The MDA had funded the discovery of the dystrophin gene, and the group was determined to turn that discovery into a cure. So when Samulski approached the group about a grant, they made him an offer.

SAMULSKI: Jude, we love the work. We love the research. But we're tired of funding academics that just publish a paper. We need something to turn into a drug.

HAMILTON: They wanted Samulski to start a company. The chairman of the MDA's board was Dr. Rodney Howell of the University of Miami. He says the group knew that Samulski didn't have much business experience.

RODNEY HOWELL: But on the other hand, he knew a tremendous lot about viruses and how they work and how they might really be effectively brought into the clinical practice.

HAMILTON: So in 2001, Samulski and a small team created Asklepios BioPharmaceutical, or AskBio. He asked a lawyer named Sheila Mikhail to run it.

SHEILA MIKHAIL: I remember Jude saying we probably won't get funding because gene therapy is an unproven technology, and there are a lot of naysayers. But it has the potential to change the world.

HAMILTON: Today, AskBio occupies a gleaming new headquarters in Research Triangle, N.C. Samulski walks me through one of the labs.

SAMULSKI: And so you see the media going around and around. That's human cells that are growing inside of a flask.

HAMILTON: Then he takes me to a less familiar device.

(SOUNDBITE OF SONICATOR)

HAMILTON: It uses sound waves to break open cells and expose the viruses inside. The company didn't have this sort of tech early on. Even so, Samulski and his team were able to create an abridged version of the dystrophin gene, one small enough to fit inside their viral FedEx truck. Then they started making deliveries - first in test tubes, then mice, then golden retrievers with the same genetic mutation Conner has.

SAMULSKI: Typically, they can't stand on their hind legs 'cause they lose their quadriceps. And they usually don't get past one year of age.

HAMILTON: But dogs who got the gene therapy did much better. And one day, Conner's parents saw a video of those dogs.

CURRAN: They were able to run and jump. We saw this with our own eyes, and we just thought, oh, gosh, if one day Conner could get a chance to get something like this. It just gave us so much hope.

HAMILTON: Samulski's company lacked the resources to bring its gene therapy to the thousands of boys with Duchenne. So in 2016, AskBio sold its treatment to the drug company Pfizer. And by early 2018, Pfizer was ready to start clinical trials. Samulski says, so was Conner Curran.

SAMULSKI: He and his brave parents volunteered to be the first to get treated with the gene therapy.

HAMILTON: As the day approached, though, Jessica had doubts.

CURRAN: I looked at my husband, and I said, Chris, are we doing the right thing for Conner? And he said, we need to be in this together, Jess, and let's think about the alternative. And the alternative is death.

HAMILTON: To Conner, the treatment with what he calls muscle juice was no big deal.

CONNER CURRAN: They put a needle in my arm for two hours.

HAMILTON: In the weeks that followed, Conner and Samulski got to know each other. The scientist played the piano for his young patient and showed him his garden.

CONNER: We talked about science and viruses and snacks.

HAMILTON: Jessica says the gene therapy worked very quickly.

CURRAN: Within three weeks, he was running up the stairs.

HAMILTON: And Conner says he kept improving.

CONNER: I can run faster. I stand better, and I can walk to Goldberg's. That's a bagel shop. It's more than two miles. And I couldn't do that before.

HAMILTON: Conner's body will never replace the muscle cells he lost, and it's not clear how long his new genes will last. But the treatment seems to work. It's now been tested on nine boys, and Pfizer is planning a much larger study for later this year. The therapy still has flaws, though. Several boys, including Conner, became ill temporarily after receiving the virus. Two ended up in the hospital. So Samulski's been working on a fix.

SAMULSKI: AAV 2, 3b, 5...

HAMILTON: The scientist stands at a whiteboard in a meeting room filled with AskBio researchers and half-empty pizza boxes.

SAMULSKI: We go to solve this. In my mind, this is the most important thing that we can do this year.

HAMILTON: As usual, Samulski has an idea.

SAMULSKI: We want to build a stop sign in here.

UNIDENTIFIED PERSON: Right.

HAMILTON: A molecular stop sign that will prevent toxic reactions to the virus. Samulski tells his team to go build one. Then he ends the meeting.

SAMULSKI: OK. Finish your pizza. Stop being lazy.

(LAUGHTER)

HAMILTON: Since then, Samulski's team has delivered the stop sign. Now they're testing it in animals.

Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.