Christopher and Jessica Curran’s 12-year-old son, Conner, has Duchenne muscular dystrophy (DMD). So does Marko, 11, the son of Paul and Seda Filenko. The Currans live in Ridgefield, Connecticut, and the Filenkos live 2900 miles to the southwest, in San Diego, California.
In 2018, both boys received an infusion of PF-06939926, an investigative gene therapy from Pfizer aimed at slowing the muscle deterioration caused by DMD. They were among the first boys in the nation to get the treatment.
Nearly 5 years later, the results are remarkably similar: not only has what Conner calls “muscle juice” stopped the progression of the degenerative disease, but the boys have even improved in some aspects.
Yet Conner and Marko are starting to plateau—and both sets of parents worry about what’s next.
“Marko has a rare duplication; 1 base pair out of 2 million got doubled on exon 11,” said the boy’s mother, Seda, who—like Conner’s mother, Jessica—has been tested and is not a carrier of DMD. “It’s extremely frustrating. We have not met anybody else with that type of mutation, nor have I been able to find any studies on it.”
On the other hand, she said, “he is walking now, and a lot of credit for that goes to the gene therapy he received. We don’t know what would have been if he hadn’t received it.”
Seda is originally from Armenia; Paul is Ukrainian. The couple met in college in Pennsylvania, and have lived for the last 8 years in San Diego, where Marko was diagnosed with DMD.
Marko was diagnosed at 5 years old only after several years of doctors, even neurologists, telling his parents nothing was wrong with the boy. It was only in November 2016, after a physical therapist referred them to a neuromuscular specialist, that a blood test was finally done; Marko’s creatine kinase (CK) level exceeded 14,000, and a biopsy confirmed he had Duchenne.
“We felt like a tsunami had hit us. I couldn’t even process what they were saying,” recalled Seda, whose younger son, 9-year-old Luka, is healthy and does not have Duchenne.
From Hopelessness to Guarded Optimism
After recovering from the initial shock, Seda and her husband began engaging with Pfizer as well as with Solid Biosciences and Sarepta Therapeutics—all 3 of which had begun pursuing gene therapy trials for Duchenne.
“Marko was originally supposed to be in the Sarepta trial but at the last minute, they changed its inclusion criteria to exclude exons 1-17. The next best bet was Pfizer, because they were farther along,” she told Rare Disease Advisor. “With Pfizer we knew he was going to be the first dosed ever at [the University of California Los Angeles (UCLA)]. There was a lot of preparation, and UCLA took over a year to prepare.”
Once Marko received the infusion, improvements were nearly instantaneous.
“A week after the infusion, he was extremely nauseated. Yet when I picked him up, he wrapped his legs around me,” Seda said. “He had never been able to do that in his entire life.”
More than 2 years later, his North Star assessment score is still 33 on a scale of 0-34, which is unusually high for a boy with Duchenne. Marko is not only walking, but can go through an entire school day without a power wheelchair.
However, his parents aren’t taking any chances. “We’ve been told to go about things as if he didn’t receive the gene therapy,” Seda said. “That means be protective of his mobility and don’t put unnecessary wear and tear on his muscles.”
The enthusiasm Marko’s parents feel about their son’s incredible turnaround is tempered by the realization that he’ll likely need to be redosed in the near future. Some issues like cardiomyopathy have already become noticeable, his father Paul said.
“This is very much not a one-and-done. This kind of medication needs to be administered at intervals of 3-5 years,” he said. “You do see a relatively dramatic improvement, but then as the years progress, it visibly goes back to previous levels. He’s not physically the same as when he was 7 years old. All these boys who were dosed 5 years ago will definitely need another dose.”
Raising Funds for Research Into DMD
Conner, who has an exon 33 deletion, was diagnosed at 4 years old in nearby White Plains, New York. His twin brother, Kyle, is healthy, as is his 10-year-old brother William.
Chris Curran, his father, works for the Lewiston, New York, municipal maintenance department. Conner’s mother, Jessica, is a first-grade teacher in Carmel, New York. Like many parents of boys with Duchenne, the Currans started a charity shortly after Conner’s diagnosis.
“The doctor told us, ‘Take your son home and love him. There’s not much you can do,’” his father said. “I had read about gene therapy and CRISPR. But he just said, ‘I’m sorry, that’s too far out in the future. Just give him a good life.’ We actually did go home and cry. It was devastating.”
For about a month, he said, “My wife and I hid under a rock. But then we said to ourselves, ‘This is no way to live. This is not going to help our son. We need to fight.’”
Refusing to accept the advice they were given, the Currans did some research and discovered the Muscular Dystrophy Association (MDA) Care Center at Johns Hopkins University in Baltimore, Maryland. There, they were told the exact opposite.
“They gave us the information and knowledge that there is hope for our son and that gene therapy was just around the corner. The MDA told us he might be able to participate in a trial within the next 3-4 years that could change his life,” Conner’s father said.
“We have firsthand knowledge of what an amazing drug [PF-06939926] really is. Honestly, all 3 of [the investigative gene therapies]—we know because they’ve measured their dystrophin levels, and their North Star assessments,” he said. “In Duchenne, you don’t get better. You just get worse, and worse, and worse. It’s a steady, predictable decline. So to actually get a little bit better is amazing.”
The Currans’ nonprofit, Kindness Over Muscular Dystrophy, has since helped raise $2 million for research, which it has channeled through MDA to fund specific gene therapy projects. One event alone, at the Captain Lawrence Brewery in nearby Elmsford, New York, attracted 600 people and raised $300,000.
Gene Therapy Helps, But It’s Not the Final Answer
The Currans have also managed to get the amount earmarked for DMD research under the Pentagon’s Congressionally Directed Medical Research Program raised from $10 million to $15 million. As such, they with all charities involved in Duchenne advocacy, including the MDA, CureDuchenne, Parent Project Muscular Dystrophy, Team Joseph, and the Jett Foundation.
“I think what’s important is that we all work together. We’re here to fight the same thing,” Chris said. “That’s how we’ll be able to really make a difference and stop this terrible disease.”
He said he hopes all 3 companies involved in gene therapy trials for Duchenne win approval from the US Food and Drug Administration, even though he knows they do not provide a cure.
“We need to figure out redosing because we’re using a viral vector. Conner has held on for about 4 and a half years, but now he’s started to slowly decline again,” he said. “Scientists and doctors are working on nonviral vectors so that you could repeat administration as many times as you’d like, as well as trying to suppress the immune system using plasmapheresis and other methods.”
Chris said that before receiving the Pfizer treatment, Conner had lots of emotional issues.
“It was really tough for Conner to see his friends and not be able to participate. Then after gene therapy, the emotional issues went away,” he said. “Obviously, it’s starting to get harder, but he can still do a little more than he could in the past. We’re still, 5 years in, really happy with his emotional well‑being. It’s not like that for every kid with Duchenne, but I want it to be—because every kid with Duchenne deserves that.”
Conner apparently knows quite a lot about his disease. Chris said the subject came up at a recent MDA event, where parents were advised to be open with their sons about Duchenne.
“You do not want him to find this on Google, or have their friends tell them, ‘My mom said that you might die when you’re 25 years old.”
“I’d rather tell him, ‘You know what, Conner? Google is a little outdated right now because of what Sarepta, Pfizer, Solid, and the Muscular Dystrophy Association are doing,” his father said. “You potentially are going to have a different life. You can see that when you look at the video of yourself before you had the therapy the video of yourself after.”
Chris added: “Google doesn’t have that information yet, but one day, they will.”