A Source of Hope

Aissam Dam’s deafness could be traced to a single gene. His otoferlin mutation destroyed the protein used by the inner ear’s hair cells to transmit sound to the brain, and so he heard nothing.

He grew up in Morocco and moved to Spain, but it was in Philadelphia that everything changed. At age 11, he was the first person in the United States to receive in vivo gene therapy for congenital deafness, at the Children’s Hospital of Philadelphia (CHOP). More importantly, for Aissam and his family, he was the first person on whom the therapy worked. One month after researchers administered a harmless adeno-associated virus to stealthily carry healthy otoferlin genes into his cochlea, Aissam could hear the children’s voices announcing each floor on the hospital’s elevator. He could hear the scissors snipping past his ear as he received a haircut. He could hear music—and everything else the world of sound has to offer—for the first time.

Learning that the procedure was successful was a powerful experience for an Ursinus alumna. Jules LaRosa Espenhorst ’19 is a project manager in CHOP’s clinical in vivo gene therapy group. There, she builds close relationships with the children and families participating in the team’s growing roster of trials.

“There’s nothing like it,” LaRosa said. “It gives you chills.”

As someone intimately involved in the screening and informed-consent process that brings patients into one of the 16 trials her group manages across seven hospital divisions, LaRosa gets to see the highs and the lows of clinical gene therapy research. She’s there with families when they’re accepted into a trial that might be their only hope to slow the effects of diseases like Duchenne muscular dystrophy, a gene mutation that causes muscular degeneration. And, perhaps more meaningfully, she’s there to offer comfort and support when a child and their family receive the devastating news that they won’t be part of a trial because of a failed test in the screening process.

Each positive result—whether a black-and-white measure like Aissam’s newfound hearing or a more modest improvement from a child with muscular dystrophy—keeps her going, pushing forward to help develop therapies that can someday give more children a brighter future.

“[Aissam’s] dad said he feels safer now that his kid can hear again, because if he calls his name when he’s riding his bike, he’ll be able to hear him. That really means everything,” LaRosa said. “That makes it all worth it on the hard days.”

LaRosa first learned about gene therapy in a bioethics course taught by Kelly Sorensen, associate dean of academic affairs and professor of philosophy and religious studies at Ursinus. With Sorensen, LaRosa and her classmates tangled with a wide range of ethical quandaries in medicine, covering everything from gestational surrogacy and medically assisted dying to human enhancement and medical experimentation.

In conversations about gene therapy, they contemplated the 1999 death of Jesse Gelsinger, a teenager participating in a trial at the University of Pennsylvania aimed at curing a rare metabolic disorder that let dangerous amounts of ammonia amass in his blood. Gene therapy is “high-risk, high-reward,” LaRosa said, but questions swirled after Gelsinger’s death, particularly around failures in the informed-consent process.

Sorensen recalls seeing LaRosa gripped by conversations that cut to the heart of medical ethics, eager for medical advances that could change lives but determined not to sacrifice moral and ethical standards at the altar of progress. Even as an undergraduate, she was “fully empathic, fully ready to take seriously the gravity of everything she was hearing,” he said.

When The New York Times wrote about Aissam’s successful procedure, LaRosa shared the story with Sorensen, pointing out the questions it raised about whether deafness is actually a condition in need of a cure—just the type of ethical debate she might have engaged in during that bioethics class.

“Dr. Sorensen really instilled in us that there are two sides to every story and everyone’s opinion should be valued,” LaRosa said.

At Ursinus, LaRosa was drawn toward public health, searching for ways she could make a difference in as many lives as possible. The public health program hadn’t yet been established, so she took as many related courses as she could on the way toward a bachelor’s in health sciences. An education centered on public health “reprograms your brain to consider the economic or social conditions that may be negatively impacting a person’s health,” she said.

LaRosa dug deeper, learning to look at public health from different angles to better understand how shortcomings could be addressed.

“Jules was swinging for the fences,” Sorensen said. “She was really interested in the health system as a whole and helping people in even greater numbers by systemic change.”

During her junior year at Ursinus, LaRosa took a public health course with Catherine van de Ruit, an associate professor of sociology, then joined her research work group. She spent two years analyzing patient safety information from an expansive qualitative dataset van de Ruit had helped create while on a postdoctoral assignment at Johns Hopkins University.

Digging through mountains of information from interviews with healthcare workers at all levels of the medical system, LaRosa was struck by the flaws that persisted. She came face-to-face with the hierarchical structure of hospitals and the ways it can create obstacles to patient safety and care.

“We’re all about engaging students’ central set of values, not just their analytical minds,” van de Ruit said. “That’s what I feel this project does for students. It fires up their sense of what the social world is like.”

For LaRosa, it helped clarify the flaws of the medical system—and the need to change things for the better. After graduating from Ursinus, she went to Thomas Jefferson University to earn a master’s in public health to learn how she could contribute to the cause.

“I had no idea I was going to end up in a rare disease field,” LaRosa said, “but I think Ursinus really fostered my interest in research.”

In turn, she helped foster the future of public health at Ursinus. She had considered creating her own major while in college, but not enough courses had yet been established to make it feasible. Encouraged by the interest shown by LaRosa and other students, the college added a health and society major in 2021.

Across the country, undergraduate interest in public health has exploded in recent years, with degree conferrals growing by more than 13 percent per year since 2001. LaRosa was “filled with pride” when she heard that Ursinus had added the major to its roster.

LaRosa saw the puzzle pieces of a public health major waiting to be put together so other students could find their own way into the rapidly growing field, Sorensen said. Ten students are now enrolled in the major. Sorensen calls LaRosa a “founding mother” of public health at Ursinus and the type of student the program aims to produce.

“She’s the kind of person we want to grapple with moral questions at the cutting edge of medical discovery,” Sorensen said.

At CHOP, LaRosa brings it all together—her moral and ethical conviction, her love of research, her drive to improve the health and well-being of as many people as possible.

The clinical in vivo gene therapy group was established in 2021, creating centralized support for divisions across the hospital to conduct gene therapy research safely and effectively. LaRosa was the first research coordinator hired to the team. Today, she trains and develops the group’s cohort of research coordinators and assistants, ensuring the group meets regulatory requirements and patients and their families always have the information and support they need. Given the circumstances in which families find themselves enrolling in a gene therapy trial, the last part is especially important.

“For a lot of parents, this is their only hope,” LaRosa said.

The work is challenging but deeply rewarding. Outcome measures are rarely as concrete as Aissam’s hearing. More often, a trial is aimed at extending a child’s life, not curing them completely.

“One of the questions I always ask anyone we’re hiring is how they’ll feel about working with sick kids,” LaRosa said. “It can definitely take a toll on you.”

That doesn’t stop her from building connections, though. On her desk she keeps an ornament given to her by a child who participated in a trial to treat GM1 gangliosidosis, a genetic disorder that destroys nerve cells in the brain and spinal cord. She listened as the boy’s mother shared his entire life story and the daily challenges of caring for a child with a rare disease. When the family visited in December for a follow-up visit, just a few days before Christmas, the boy gave her an ornament he had painted to show his appreciation.

“It’s the little things that make this job worth it,” LaRosa said. “I keep the ornament in my office to remind me to keep going even when times are tough.”