“Sorry if I keep my phone close while we talk, but I’m waiting for a call because they have to deliver some cells,” says Dr Francesca Ferrua as she welcomes us into one of the offices of the Pediatric Immunohematology Unit at IRCCS San Raffaele Hospital. The Unit is directed by Professor Alessandro Aiuti, Full Professor of Pediatrics at UniSR and Deputy Director of the San Raffaele–Telethon Institute for Gene Therapy (SR-Tiget).
A pediatrician and medical director, Dr Ferrua completed her entire training at UniSR: she graduated from our Faculty of Medicine and Surgery (current Dean: Prof. Sonia Maria Rosa Levi), then went on to specialize in Pediatrics under the supervision of Professor Aiuti, and finally obtained an International PhD in Molecular Medicine (current Coordinator: Prof. Alessandra Bolino), with a curriculum in Basic and Applied Immunology and Oncology (current Curriculum Heads: Prof. Paolo Ghia and Prof. Mirela Kuka), under the supervision of Dr Anna Villa.
Dr. Francesca Ferrua
From the beginning of her specialization and for the following 15 years, Dr Ferrua followed the clinical studies on the safety and efficacy of gene therapy for Wiskott–Aldrich syndrome, a rare genetic immunodeficiency.
And it was just last December 9 that the news broke that the Food and Drug Administration (FDA) approved this gene therapy in the United States. Only a few weeks earlier, the therapy had also received a positive opinion for marketing authorization from the EMA, the European Medicines Agency.
This extraordinary achievement is the result of a path that intertwines basic research, conducted in the laboratories of SR-Tiget, and clinical experimentation carried out at IRCCS San Raffaele Hospital.
A 35-year journey, during which an entire generation of scientists worked to understand the biological basis of the disease and to find an alternative to bone marrow transplantation—the standard therapy for people with Wiskott–Aldrich syndrome—for those who cannot benefit from a compatible family donor.
Among these scientists is Dr Ferrua, whom we met to hear the story of a UniSR alumna who became first a physician and then a researcher with a clear goal: to change people’s lives.
When, at the end of high school, I had to choose a university, I had very few doubts once I learned about the San Raffaele model: hospital, university, and research laboratories all concentrated on the same campus and closely interconnected.
This synergy was—and still is—something unique compared to other clinical–academic settings, and at the time it convinced me to enroll at UniSR. Back then, there were 900 applicants for only 90 places: I was convinced I wouldn’t make it, and yet here I am.
Studying here was a wonderful adventure: the relationship with professors was always direct, and my classmates and I were exposed to clinical practice and laboratory work from the very beginning. We took part in journal clubs, lab activities, group projects… teaching was always very interactive.
It happened gradually. Around the fourth year of medical school, I started attending the Hematology and Bone Marrow Transplant and Oncohematology Unit, directed by Professor Fabio Ciceri. Over time, however, I became increasingly interested in the experiences of children receiving transplants or participating in the first gene therapy studies.
That was when I began to feel that I wanted to specialize in pediatrics. I ultimately carried out my degree thesis in the Pediatric Immunohematology Unit at San Raffaele, under the supervision of Professor Maria Grazia Roncarolo and Professor Aiuti, and then continued with my specialization in Pediatrics.
It was 2010 when Professor Aiuti and Professor Roncarolo involved me in the clinical studies to test this new gene therapy for Wiskott–Aldrich syndrome, which had shown promising results in the preclinical phase.
Even today, I feel privileged: I was able to follow the process from the very beginning—from drafting the clinical protocols, to enrolling the first patients, to the first results in 2019 that offered hope. I will probably never have a similar experience again in my personal and professional life.
But the real success is not just the graphs and a thick dossier of data to present to regulatory authorities.
The real success is seeing patients grow up, attend school, play sports, and look at photos of their birthday parties with friends. These are normal experiences for a healthy child, but incredibly important milestones for those born with a severe disease like Wiskott–Aldrich syndrome.
Rather than bad moments, I would speak of difficult ones. There were challenges related to disease-related complications in some patients, but from each of these situations we gained valuable lessons to improve treatment management.
Perhaps the most difficult moments of all were two: one when the first pharmaceutical company that had taken on the project decided to stop investing in it; the other when a second company withdrew just a few days before submitting the dossier to the regulatory authorities. That was the most painful moment of the entire journey: we had a safe and effective treatment, but we risked no longer being able to offer it to patients.
How did you manage to reach approval?
Fortunately, the Telethon Foundation took the project back in hand, allowing us to start again and prepare a new, updated registration dossier.
This past year has been very intense: since we applied in parallel to both the EMA and the FDA, in recent months we have received inspections at our Unit from both authorities.
It was another challenging but extremely educational moment, which also reaffirmed something I already knew: our clinical trial was conducted with great rigor, and this was crucial to obtaining approval.
Because, as I explained at the beginning, here basic research, preclinical development, and clinical practice are deeply integrated and can rely on a set of consolidated skills and knowledge. This constant dialogue between the laboratory and the clinical setting is the real strength of the San Raffaele model.
I felt that my training was not complete. I had a solid clinical background, but I wanted to experience basic research firsthand. I felt—and still feel—that it is necessary to fully understand clinical problems and to actively seek concrete solutions.
For this reason, I also pursued a PhD in basic and applied Immunology and Oncology, again at UniSR. It was a demanding choice, but for me it was necessary to further develop my professional path.
Always aim high. Not looking down from above, but truly looking upward.
Never give up in the face of difficulties; always try to step outside your comfort zone, knowing that you won’t always succeed, but that it’s worth trying. This is, after all, the spirit of San Raffaele’s original vision: a place where professionals carry out excellent clinical work, education, and research to change people’s lives. It is a model that works and continues to deliver results.
Be resilient and don’t be afraid of hard work.
The path is demanding, but when you reach the top, the view makes it all worthwhile—much like climbing a mountain: for a long stretch, all you see is rock, rock, rock, until you finally reach the summit and a breathtaking panorama opens up before you.
This long journey—from basic research on Wiskott–Aldrich syndrome to the approval of gene therapy—has been much the same: many years of rock, rock, rock, culminating in a view from above that reveals a new possibility for patients and their families.
This concludes the tale by Dr Ferrua: the testimony of a scientist who believes in the value of knowledge that leads to innovation—innovating through knowledge—which is the goal we work toward every day here at UniSR.