Receiving a diagnosis for an ultra-rare genetic disease often leaves families in medical isolation. For children with CHOPS syndrome—a complex, multi-organ neurodevelopmental condition—treatment options remain severely limited. Historically, medical systems have treated rare diagnoses as final verdicts rather than starting lines for scientific inquiry. Without commercial incentives for large pharmaceutical developers, families and clinicians face an uphill battle to fund basic research, understand disease mechanisms, and identify viable therapies.
The CHOPS Foundation (Fondazione CHOPS Malattie Rare ETS) emerged to change that reality. Founded by parents determined to build a clear path toward a cure, the organization unites global researchers, leverages modern technology, and funds targeted studies to accelerate drug development. In this interview, Manuela Mallamaci, President and Founder of the CHOPS Foundation, discusses how patient advocacy drives medical innovation, the role of artificial intelligence in rare disease research, and the urgent push to deliver therapies to children worldwide.
Q: The CHOPS Foundation began after a grassroots campaign in Italy inspired by your son Mario. How did that personal journey evolve into an international foundation dedicated to scientific research?
Manuela Mallamaci: Mario was born in 2021, in the middle of the pandemic, and for his first months we believed he was a healthy baby. At around five months, we noticed he was less responsive than other children. Soon after, a pediatrician suggested a heart check, and we discovered a severe congenital heart defect that required two open-heart surgeries. After about a year and a half of genetic testing, we finally had a name: CHOPS syndrome, an ultra-rare condition with only 13 cases described in the medical literature and fewer than 40 known worldwide.
I am a researcher by training, with a PhD in astrophysics, so the unknown does not paralyze me. A few days after the diagnosis, I spoke with Lainey Moseley, the mother of the first patient ever diagnosed, and then with Dr. Ian Krantz, who described the syndrome in 2015. I asked him one question: is a cure possible? He said yes. It would be difficult, but possible. That was enough for me. I believe in science, and I have seen what it can do when the right people and resources come together.
We opened a social media page to tell Mario’s story and launched a fundraising campaign, “Un aiuto per Mario e non solo” (“Help for Mario, and not only for him”). Thousands of people responded. At that point, the natural next step was to build a transparent, recognized organization. In May 2023, my husband Gianni and I founded the CHOPS Foundation, the first and only non-profit in the world dedicated to this syndrome. From the beginning, we chose an international approach: with so few patients spread across continents, no single country could move the science forward alone.
Q: You often emphasize that a diagnosis should be the starting point rather than an end point. How does that philosophy shape your approach to rare disease research and clinical care?
Manuela Mallamaci: There is still a very strong belief that “rare” means “incurable.” When we received Mario’s diagnosis, the implicit message was that we were already doing everything that could be done. I refused to accept that.
A diagnosis gives you something precise to fight against. Today we know that CHOPS is caused by mutations in a single gene, AFF4. Once you know the molecular cause, you can study the mechanism, build disease models and design therapies that target it. Palliative care and symptom management remain essential, but they cannot be the only horizon.
This philosophy shapes everything we fund. We invest in basic research to understand biology, and in parallel we pursue therapeutic strategies from day one, rather than waiting for the basic science to be “complete.” It also shapes how we see families. In ultra-rare diseases, the patient is not only a recipient of care but an active participant in the research process, through samples, data and shared clinical experience.
Q: Rare disease research often struggles with long timelines and high costs. How are your partnerships, such as the AI-driven drug discovery program with Unravel Biosciences and your work with The Jackson Laboratory, accelerating the search for treatments?
Manuela Mallamaci: We work on two complementary tracks, because running them in parallel increases our chances of reaching a safe and effective therapy sooner.
The first is drug repurposing. With Unravel Biosciences, we used an AI-driven platform to compare data derived from patients’ cells against roughly 20,000 drugs already approved for other conditions. This narrowed the field to a shortlist of candidates, which are now being validated in patient-derived cells. Because these molecules have already been tested for safety in humans, this path could be significantly faster than developing a new drug from scratch.
The second track is more ambitious: antisense oligonucleotides (ASOs), developed in collaboration with The Jackson Laboratory. ASOs are short, custom-designed RNA-like molecules that act directly on the altered gene expression at the root of the syndrome. Rather than treating symptoms, they aim to correct the problem at its origin. It is a therapy designed specifically for children with CHOPS, and it shows that even for a condition this rare, we can aim for a truly targeted treatment.
Alongside these, we fund basic research and disease models at centers such as Children’s Hospital of Philadelphia, Baylor College of Medicine, UT Southwestern Medical Center and the University of Essen. We are also contributing to the first biobank dedicated to CHOPS and AFF4 mutations. In total, we have funded six research projects with over €400,000, entirely through donations.
Q: In 2024, the foundation hosted an international symposium at Children’s Hospital of Philadelphia, followed by conferences in Europe. Why is bringing clinicians, researchers, and families into the same room critical for advancing translational medicine?
Manuela Mallamaci: In a disease with about 40 known patients, every family holds a piece of the puzzle, and every researcher holds another. Translational medicine happens when those pieces meet.
After Philadelphia in 2024, we brought the symposium to Europe for the first time, at the University of Milan in June 2026. Over three days, geneticists, molecular biologists and clinicians shared their latest findings, and families met researchers face to face, including in private one-to-one conversations. Something changes when a scientist who studies AFF4 in cell lines meets the children whose lives depend on that work. Several of our researchers told us it gives their work a deeper sense of purpose and urgency.
These meetings also generate new science. In Milan, it became clear how closely CHOPS is linked to Cornelia de Lange syndrome at the molecular level. We also discussed how the mechanism disrupted in CHOPS is the same one involved in some childhood leukemias. Understanding an ultra-rare condition can illuminate much more common ones. That is why we opened the symposium to other rare diseases, patient associations and institutions.
Q: For ultra-rare diseases, patient populations are small and geographically scattered. How does the foundation connect affected families across different continents, and how does this global community support your research roadmap?
Manuela Mallamaci: We established an International Family Committee, which is often the first point of contact for families who have just received a diagnosis. When you are told your child has a condition shared by only a few dozen people on Earth, the sense of isolation is overwhelming. Knowing that another family on another continent has walked the same path changes everything.
This network is also the backbone of our research. Patient samples from different continents made the cell lines and drug screening possible. Shared clinical histories help researchers understand how the syndrome evolves over time. Families’ priorities guide what we fund: for many of them, the goal is not an abstract “cure” but concrete milestones, such as reducing the respiratory problems that weigh so heavily on daily life, walking, communicating and living with greater independence. A global community also gives our work visibility, and visibility attracts researchers, partners and donors.
Q: Looking at the foundation’s funded research projects, what key milestones must the scientific community achieve next to translate laboratory findings into clinical therapies for children affected by CHOPS syndrome?
Manuela Mallamaci: The next milestones are clear. First, we need to establish a well-defined CHOPS phenotype at both the cellular and animal level: reliable models that show exactly how AFF4 mutations alter cell function and development. Second, we need to narrow down the most promising therapeutic candidates emerging from our two parallel tracks, drug repurposing and antisense oligonucleotides. Finally, we must strengthen the infrastructure that any future clinical trial will require: the biobank, robust disease models, and a deeper understanding of how CHOPS progresses over time. The publication of the first GeneReviews chapter on CHOPS this year, authored by Dr. Kosuke Izumi, winner of our 2024 research grant, is an important step in that direction.
But there is a milestone that does not depend on science alone. A foundation like ours can carry research up to the preclinical stage. To turn those results into therapies available to children, we need institutions, regulators and industry partners to step in, including when a promising drug is off-patent and offers little commercial return. In ultra-rare diseases, the number of patients cannot be the only criterion for deciding whether research is worth pursuing. Every child deserves that chance, and what we learn from CHOPS can benefit many others.
The fight against rare genetic diseases requires bold advocacy, scientific rigor, and international collaboration. As demonstrated by the CHOPS Foundation, patient-led organizations are no longer passive observers in medical science; they are active drivers of research agendas. By funding biological investigations, adopting artificial intelligence for rapid drug screening, and establishing international networks, families are creating the infrastructure needed to address complex multi-organ conditions.
Transforming the trajectory of CHOPS syndrome offers a practical blueprint for the broader rare disease community. When researchers, clinicians, and advocacy leaders work together with urgency, therapeutic discovery moves faster and reaches patients sooner. Through transparent research partnerships and focused community support, the CHOPS Foundation continues to turn hope into actionable science, ensuring every child receives the opportunity for early diagnosis, targeted treatment, and a better quality of life.
To learn more visit https://fondazionechops.com/en/
