“Let us not forget the most vulnerable”: A Conversation with Prof. Christoph Klein, Professor and Chair, Dr. von Hauner Children's Hospital at Ludwig Maximilians University

Children with rare diseases are often described as the orphans of medicine—overshadowed, misdiagnosed, and forced to endure a relentless odyssey from doctor to doctor. Many of these conditions remain incurable, leaving affected children and their families with little hope for a better future. However, through increased research efforts and robust international cooperation, this grim fate can be transformed. The Care-for-Rare Foundation stands at the forefront of this mission, working across national borders to provide hope for a cure to every child, regardless of their background or financial means. In this conversation, we speak with Prof. Christoph Klein, a leading figure in pediatric medicine and the visionary founder of the Care-for-Rare Foundation. His insights reveal how collaborative, cross-disciplinary research is reshaping the future of rare disease treatment and bringing us one step closer to a world where no child is left behind.

Prof. Klein, thanks for joining us. Could you share a bit about the Care-for-Rare Foundation and what led you to establish it?

Christoph Klein: First, I’d like to thank you for the invitation. It’s a pleasure to be here. I wear several hats—I'm the Chair of the Department of Pediatrics at LMU Munich, and one of my most personal endeavors is the Care-for-Rare Foundation, which I founded to support children with rare diseases. Unlike many other foundations initiated by parents or patients, Care-for-Rare was established from a clinical and scientific perspective, with the goal of understanding the root causes of rare diseases and developing targeted therapies based on this knowledge. Beyond that, we believe that insights gained from studying rare diseases can also benefit patients with more common conditions.

Over the past 15–16 years, the foundation has operated across a broad spectrum of activities, with research as its primary focus. Through the International and Global Care-for-Rare Alliance, we collaborate with more than 80 countries, connecting pediatric hospitals and research institutions worldwide.

To foster the next generation of physician-scientists, we also launched the Care-for-Rare Academy, ensuring young researchers are equipped to lead in the field. We also established Care-for-Rare Aid, dedicated to helping patients who lack financial access to medical treatment. Additionally, we offer the Care-for-Rare Awards, which provide funding for innovative scientific projects and recognize one outstanding researcher each year to encourage more scientists to focus on rare diseases rather than exclusively on areas like cancer or Alzheimer’s research.

The Care-for-Rare Foundation has played a crucial role in identifying new genetic causes and developing therapies for rare diseases. Can you share some recent progress?

Christoph Klein: Patient stories best illustrate the critical importance of rare disease research. One such story is Sarah, a young girl from northern Germany who suffered from a severe and rare form of pulmonary alveolar proteinosis (PAP). She required lung lavage procedures every four weeks—undergoing general anesthesia and intubation each time—to temporarily relieve the fluid buildup in her lungs.

When I met Sarah, all known causes of PAP had been ruled out. Recognizing that she likely had an unidentified condition, we invited her and her family to participate in a research project to uncover the root cause of her illness. Through a series of genetic, genomic, and functional studies, we discovered that she had a mutation in the OAS1 gene (oligoadenylate synthetase 1), which plays a key role in fighting viral infections in the lung. This mutation disrupted her immune system’s balance, rather than affecting her lung cells directly.

This finding completely transformed our approach to her treatment. Since hematologists are experienced in performing allogeneic blood stem cell transplantation, we proposed using this technique to replace her defective immune cells. The procedure was remarkably successful—within four to five weeks, Sarah no longer needed an oxygen tank or lung lavage, and she has remained symptom-free ever since.

Sarah’s case underscores why research on individual patients is so vital. Understanding the precise genetic and immunological mechanisms behind rare diseases can lead to personalized, life-changing therapies that would otherwise be impossible.

That’s an incredible story, and it really highlights how unlocking the genetic basis of a disease can completely change a patient’s life. But as you know, moving from discovery to treatment isn’t always straightforward. If you could change one major bottleneck in the rare disease drug development process today, what would it be and why?

Christoph Klein: That’s a tough question. As a trained hematologist-oncologist, I’ve seen firsthand how the field of oncology transformed cancer from a fatal disease into a curable one. Eighty years ago, every child diagnosed with cancer was destined to die. Then, courageous physicians refused to accept that fate and began experimenting with toxic drugs to treat acute lymphoblastic leukemia. The first remissions weren’t sustainable, but through global collaboration and clinical trials, oncologists systematically improved treatment protocols. Today, we cure over 80% of children with cancer.

However, this type of clinical trial model is now nearly impossible due to increasingly complex and costly regulatory frameworks. While regulations are intended to protect patients, they have become so restrictive—especially in Europe—that conducting these critical studies is extremely difficult. We need to reassess whether all of these regulatory barriers are truly necessary or if they inadvertently slow progress and prevent life-saving treatments from reaching patients.

Funding is another critical issue. Clinical studies are expensive, and rare disease research is often overlooked because it isn’t commercially profitable. But we must not abandon children simply because their diseases are rare. Their lives have the same dignity and worth as any other patient. We have an ethical obligation to ensure that every child, no matter how rare their condition, has access to innovative treatments and the best possible care.

Thank you for highlighting these major bottlenecks. As a physician and trained oncologist, how do you see rare disease and other diseases such as cancer might intersect?

Christoph Klein: Rare diseases are deeply connected to more common disorders like obesity and cancer. Pediatric cancer, in itself, is a spectrum of rare diseases, and what we learn from monogenic rare diseases often has implications for adult health. For example, around 15% of children with cancer have an underlying rare genetic mutation that predisposes them to the disease—these findings are critical not only for pediatric oncology but also for understanding cancer risk and progression in adults.

I strongly believe that we need to take a broader, cross-disciplinary approach to medicine. Instead of rigidly categorizing diseases into traditional subfields, we should reframe our understanding based on genetic, functional, and cellular mechanisms rather than outdated classifications from a century ago.

We are at a pivotal moment in medical history, where our growing mechanistic understanding of disease can finally enable truly personalized medicine. We need to ensure that every patient, regardless of age or condition, receives the best possible therapy—tailored to their genetic and biological profile.

February marks Rare Disease Day. If you had the attention of our global readers, whether biotech CEO, venture capitalist, or other ecosystem stakeholders for just one minute, what would be your call to action?

Christoph Klein: Raising awareness cannot be limited to February 28 or 29—it must be a year-round effort. We need to share patient stories, engage with policymakers, and speak with those responsible for shaping our societies.

Let us not forget the most vulnerable among us—children with rare diseases who still lack hope for effective therapies. Today, we have unprecedented scientific knowledge across medicine, biotechnology, and computational sciences. We have the tools to change their destiny, to give them the hope of a healthy future. But we cannot do it alone. We must work together—across disciplines, institutions, and countries—to drive innovation and accelerate treatments. The time to act is now. Let’s seize this opportunity and make a lasting impact on the lives of those who need it most. At the end of the day, what could be more meaningful than dedicating your professional life to ensuring that children with rare diseases can lead happy, healthy lives?