The stage is set, and Jake Marrazzo is at its center. On his mark beneath the bright lights, he extends his arms, projects his voice, and speaks his lines with a magnetic confidence.

Beside his costars, Jake doesn’t draw attention because he’s in a wheelchair. He draws attention because it’s impossible to take your eyes off him when he’s on stage. Every scene he’s in showcases him fully immersed in his character—the sign of a truly talented performer. And he keeps making everyone laugh.

A sense of humor might be difficult to maintain for others who have experienced the challenges that Jake has. But everyone who knows how positive Jake is also knows that performing in front of a crowd of smiling faces comes as natural to him as his will to succeed.

Jake was diagnosed with Duchenne muscular dystrophy, or DMD, at eight years old. DMD causes the body’s muscles to deteriorate and become weaker over time. This occurs because of an absence of dystrophin, a protein that allows our muscles to function and our bodies to move.

DMD is a rare genetic disease. The DMD gene is located on the X chromosome, making Duchenne muscular dystrophy an X-linked disease. Males are more likely to be affected—about 1 in 3500 births—because they have only one X chromosome. Some boys may develop the disease as the result of a spontaneous, non-inherited mutation, but most, Jake included, inherit the abnormal gene from their mothers.

“Growing up, Jake was a very smart and creative kid,” says Sheryl Marrazzo, Jake’s mom. “He loved putting puzzles together and would draw all the time.”

He was also very active and loved playing basketball. Whenever he played, though, Jake noticed he had trouble keeping up with his teammates.

“After I was diagnosed, it was upsetting to learn about this disease,” says Jake. “At the same time, I was happy to know why I was going slower than the other kids, that there was a reason for the things I felt I couldn’t control. That was almost a relief.”

In the seven years since his diagnosis, Jake has spent countless days in the hospital, tried various medications, and lost his ability to walk, now using a wheelchair full-time. Through all this, he looks up, choosing not to dwell on what he can’t change. He focuses instead on what he loves, like being on stage, and the difference he can make for others, like the impact his charity, 4 Jake’s Sake, has had on the lives of children less fortunate than him.

Yet, there is one thing he does wish could change: the limited treatment options for DMD. In a letter to the scientific community, Jake describes how life-changing a truly effective treatment for DMD would be—and not just for himself, but for his four-year-old nephew Tyler, who was recently diagnosed with DMD.

The face of hope

“Dear Scientist,” reads Jane Owens, a medical researcher currently studying Duchenne muscular dystrophy at Pfizer, a biopharmaceutical company in Cambridge. “My name is Jake Marrazzo and I’m 15 years old…”

As Jane reads on, she learns the story of a young boy living with a disease that is slowly limiting his motor functions. Even though Jake’s positive attitude shines throughout, many details, like wanting to always be able to perform on stage, remind Jane of other young boys with DMD that she’s met throughout her research career.

“My team and I are working to help these boys however we can,” she says. “Whether that’s trying to give them a little more time before they can’t walk, or trying to help them maintain strength in their arms so they can push their own wheelchairs or continue to play games on their devices, it all matters toward their quality of life.”

Jane’s interest in the natural sciences stems from her father, a biology teacher. He often challenged his children to learn how things work, a mission she’s carried with her throughout her career. Before moving to England at age eight, she spent several years living in Africa and returned there for a visit after she finished her PhD. On that trip, she encountered many people suffering from diseases that had no treatments whatsoever.

“I remember thinking, ‘I really want to help people,’” says Jane. “’I want to work in an area of study where there’s no medicine available for patients.’”

This aspiration brought her to the U.S., where she began her drug development career studying bone and muscle diseases. In 2008, she helped establish Pfizer’s Orphan and Genetic Disease group (which later became the Rare Disease Research Unit) to understand the mechanisms underlying muscle-wasting conditions, like Duchenne muscular dystrophy. Like the patients Jane met in Africa, DMD patients had few to no treatment options at that time—and this only reinforced her commitment to finding ways to help them.

Over the past decade, she and her team have been hard at work. They’re working with an antibody developed to build muscle mass and improve muscle quality. Their efforts have culminated with this antibody being tested in an ongoing clinical trial for boys with DMD. This is only one of several disease-management approaches that scientists are working on for boys with DMD today.

In addition to this, Pfizer has recently initiated a gene therapy clinical trial for DMD, moving the decades-long research initiated by Bamboo Therapeutics from bench to bedside. Since DMD results in a lack of dystrophin, scientists think that supplying a new gene that codes for a working form of dystrophin should restore its production in muscle cells, thus preventing further muscle breakdown.

“We’re essentially trying to replace the mutated gene to restore dystrophin production in these boys’ muscle cells,” says Jane. “It’s satisfying to be working on something that could be disease-modifying. It’s cutting-edge science, and we have a lot of hope that we’ll be successful.”

Meeting face to face 

It’s a sunny May afternoon when Jake and his parents, Sheryl and John, join Jane at the Pfizer research site in Kendall Square. After reading Jake’s letter, Jane can’t wait to speak to the selfless, self-assured young man behind it. And as someone with DMD, Jake wants to meet a scientist searching for the breakthroughs that could potentially change his life.

After introductions, Jake talks about his involvement in the drama society and his hope to join the student advisory committee. He shares how open he is about his condition. To him, it’s important to educate as many people about Duchenne as possible. Jane agrees.

“It sounds like you’re a great advocate for Duchenne and its awareness, which is important,” says Jane. “At Pfizer, we believe it’s crucial for people in the community to understand what this disease is. The more they realize, the more they can help.”

“Exactly,” says Jake. “When I was writing my letter, I was also thinking of myself as a role model. I know there are some younger kids out there with Duchenne, like Tyler, who I really want to set an example for. I want them to watch me and think, ‘Oh my god, if he can do all this stuff, so can I.’”

Jake and his family ask Jane about her team’s progress in the lab. She describes how her team is studying skeletal muscle cells and heart muscle cells—derived from DMD patient samples that patients have generously made available for research-use—to look for new ways to attack the disease. They also talk about how advances in therapies that address the symptoms of DMD are improving the quality of life for many DMD patients.

“Even without a cure, we prefer to look at the positive side,” says Jake’s mom, Sheryl. “Today, there are people with Duchenne living much longer. They’re going to school, getting married, having children. We know someone [with DMD] who’s going to be a grandfather.”

Jake’s optimism has had a domino effect. Seeing their son grow into such an exemplary young man has made the Marrazzos proud. And in only the short time they’ve been speaking, Jake has further energized Jane in her mission.

“Your maturity, compassion, selflessness, and bravery are inspirational to me and my team,” says Jane. “We’re dedicated to battling Duchenne. Knowing that we’re working to improve the lives of boys like you makes it all the more worth it. So thank you.”

“You’re very welcome,” says Jake, shaking her hand.

After saying goodbye to the Marrazzos, Jane heads back to the lab. There’s work to do.

To read Jake’s full letter, click here.