​The Oxford-Harrington Rare Disease Centre represents a transatlantic alliance created to bridge academic research and drug development for rare diseases. Founded in 2019 by the United Kingdom’s University of Oxford and the Cleveland-based Harrington Discovery Institute, the center leverages Oxford's world-class rare disease research and Harrington's pharmaceutical-scale expertise to address translational challenges and advance promising therapies for rare diseases lacking approved treatments. We spoke to Matthew Wood, director of the Oxford-Harrington Rare Disease Centre, about the challenges of rare disease drug development, the resources the center brings to address them, and the mechanisms it has established to accelerate therapeutic development.

Floyd Stewart was diagnosed with late-stage nasopharyngeal carcinoma, a rare, fast‑growing head and neck cancer that advanced quietly until it appeared as a bulge in his neck. The diagnosis became a struggle for his entire family as his treatments reshaped family life for Floyd, his wife Monique, and their four children. We spoke to the Stewarts about how they navigated the healthcare system, the strain the experience put on their family, and why today they are rare disease advocates seeking to raise awareness for the rare cancer and help other families dealing with similar problems. 

There have been great advances in the treatment of cystic fibrosis, but nevertheless it remains a progressive, life‑shortening genetic disease as many patients still don’t reach normal function and continue to face infections, exacerbations, and impaired quality of life. Siona Therapeutics is building a new generation of small‑molecule therapies that directly stabilize the region most affected by the most common mutation underlying the disease for the roughly 90 percent of patients who carry the defect. We spoke to Mike Cloonan, CEO of Sionna, about its experimental therapy that stabilizes the misfolded protein at the heart of the disease, its exploration of combinations with existing and proprietary therapies, and its $219 million IPO in February, despite the difficult financing environment for development-stage biotechs.

As a college student, Megan Beaulieu first noticed her smile faltering and her arms growing weak, which she chalked up to stress and exhaustion. Within weeks, her symptoms had worsened to the point that she could no longer lift her hands to wash her hair—a progression that led to her diagnosis of myasthenia gravis, a rare autoimmune neuromuscular disease. Since then, she has taken to TikTok to share her journey. We spoke with Beaulieu, who now works as a project manager at a construction firm, about living with myasthenia gravis, her decision to use social media to educate and inspire others with the condition, and how she learned to advocate for herself before advocating for others.

Dermatomyositis is a rare multi-organ autoimmune condition that primarily affects the skin and muscles. It causes fatigue, muscle weakness, and painful skin rashes. Treatment for the condition has long centered on the use of chronic systemic steroids, which can carry long‑term toxicity. Priovant is developing brepocitinib, a dual TYK2/JAK1 inhibitor originally developed at Pfizer to treat the condition. We spoke to Ben Zimmer, CEO of Priovant, about the company's experimental targeted therapy to treat dermatomyositis, how its relationship with its parent Roivant frees it from reliance on the capital markets, and the broader potential of n the treatment.

Veteran biotech investors Steven St. Peter and Luke Evnin launched Vie Ventures to bridge traditional venture capital with disease-focused philanthropy to target autoimmune and immune-mediated diseases. The fund partners with large patient organizations, such as the Lupus Research Alliance and Scleroderma Research Foundation, to invest in series B and C rounds in clinical-stage companies. We spoke to St. Peter, co-founder and managing director of Vie Ventures, about the firm’s investment model, its initial focus on immune-mediated diseases, and its work with major patient organizations.

When Nikki McIntosh’s son Miles was less than a year old, he was diagnosed with a form of the rare neuromuscular condition spinal muscular atrophy. Since then, she has needed to learn how to manage the complexities of her own life while managing Miles’ care, coordinating his providers; and navigating the medical, financial, and emotional aspects of raising a child with a rare disease. McIntosh has shares her experience in a book intended to help others new to the journey of caring for a child with a rare disease. We spoke to McIntosh, author of “Rare Mamas: Empowering Strategies for Navigating Your Child’s Rare Disease,” about her book, the medical, emotional, and logistical challenges faced by rare disease families; and the importance of making time for self-care.

Spinocerebellar ataxia is a group of inherited, heterogeneous neurodegenerative diseases affecting coordination, speech, and vision. There are currently no FDA approved therapies for the more than 50 known types of SCA​, but there is a growing pipeline of therapeutic candidates. We spoke to Andrew Rosen, CEO of the National Ataxia Foundation, about the challenges of developing therapies for spinocerebellar ataxia, the critical role of patient-led organizations in early-stage research and advocacy, and the recent surge of therapeutic activity targeting these neurodegenerative conditions.

A recent report from the health research network and real-world data platform TriNetX argues that by aggregating electronic health records, billing claims, and registry data across hundreds of healthcare sites makes it possible to study rare diseases more efficiently. Doing so could enable access to enough patient data to conduct meaningful research, which is often impossible through traditional clinical trials. We spoke to Jeff Brown, chief scientific officer of TriNetX, about how real-world data can address common challenges in rare disease research, the hurdles that need to be addressed, and how advances in AI could revolutionize rare disease research by using this data to identify patients and unlock insights.

Huntington’s disease is a rare, inherited neurodegenerative disorder caused by a type of genetic mutation known as a trinucleotide repeat expansion, which leads to the production of a toxic protein that causes progressive brain cell loss. Vico Therapeutics is developing an experimental antisense oligonucleotide to treat the condition. Because the therapy targets the repeat expansion itself, rather than a specific gene, it may have applications across a broader set of so-called polyglutamine diseases of which Huntington’s is one. We spoke to Prarthana Khanna, vice president of corporate business development and strategy for Vico, about Huntington's disease, the company’s experimental ASO to target the disease, and why it has the potential to address multiple neurological diseases. 

After Philippa Ward’s five-month-old son, Thomas, suffered infantile spasms, he was soon diagnosed with tuberous sclerosis complex—a rare genetic disorder that causes noncancerous tumors to form on various organs, including the brain. Thomas experiences near-daily seizures, cannot communicate verbally, and, due to delayed motor skills, often requires the use of a wheelchair. We spoke to Ward about her journey as the mother of a child diagnosed with tuberous sclerosis complex, the challenges posed by the condition’s complexities, and how she found both a community of support and her own voice as an advocate.

Partnerships between biopharmaceutical companies and patient organizations can play a critical role in improving access and outcomes for people with rare diseases. However, to do so, companies must listen to patient communities and address the unique challenges they face. We spoke to Laura Russo, U.S. patient engagement lead for Pfizer, discusses how the company’s patient-facing teams work to bridge health systems and patient communities, how they help people with rare diseases navigate the healthcare system, and how they improve access through customized approaches ranging from providing transportation to care for people with sickle cell disease to providing education and support to community health workers.

Hunter syndrome is caused by the body’s inability to produce a critical enzyme needed to break down cellular waste. The condition can cause damage to organs throughout the body as well as to the brain. A new generation of therapies in development, including a gene therapy currently under review by the U.S. Food and Drug Administration, that has the potential to address the neurological symptoms of the disease. Still, patient advocates have been frustrated by regulatory delays and are seeking to push the FDA and Congress to take action. We spoke with Kristin McKay, CEO of the Hunter syndrome patient advocacy organization Project Alive, about the need for new therapies, the importance of early detection, and the patient community’s concerns with regulatory delays in approving needed treatments. An editor’s note: Since recording this podcast, the FDA granted accelerated approval to Stealth Biotherapeutics’ Forzinity for Barth syndrome, which is referenced in the discussion.

Developmental and epileptic encephalopathies are a group of rare disorders that are characterized by frequent seizures that often don’t respond to existing medications. These are complex conditions that involve progressive cognitive and behavioral manifestations that can pose significant burdens on patients and their families. In both clinical practice and within the biopharmaceutical industry, there has been a tendency to focus on seizure control, while often overlooking the non-seizure burdens of developmental and epileptic encephalopathies. We spoke to Amelie Lothe, global medical community head for rare epilepsies at UCB, about the need to view these developmental and epileptic encephalopathies as complex neurodevelopmental conditions, the need to go beyond seizure frequency when it comes to clinical trial outcome measures, and what drug developers can do to improve their research focus to include broader patient and caregiver experiences.

Achondroplasia is the most common form of dwarfism. Beyond short stature, people living with achondroplasia can experience serious health complications, including compression of the brainstem and upper spinal cord due to impaired development of the skull. Tyra Biosciences is developing a next-generation medicine to precisely target FGFR3, an overactive growth factor that causes achondroplasia. We spoke to Todd Harris, CEO of Tyra Biosciences, about the company’s experimental once-daily, oral medicine for achondroplasia; what’s known about it from studies conducted to date, and why he believes it will offer competitive advantages over existing therapies.

Recurrent high-grade glioblastoma is a rare and aggressive brain tumor, which today is generally treated with surgery and chemotherapy. Outcomes are poor, with survival ranging from three to nine months and five-year survival rates less than 10 percent. Candel Therapeutics is developing viral immunotherapies that both kill tumor cells directly and enlist the patient’s own immune system in the fight against cancer. It’s experimental therapy CAN-3110 uses a modified herpes simplex virus that carries a viral gene that is designed to allow the virus to replicate in tumor cells while avoiding healthy cells. We spoke to Paul Peter Tak, president and CEO of Candel, about its viral immunotherapy, how it works, and what clinical studies have shown to date. 

While there has been enormous innovation in the treatment of cancer over the past two decades, much of this has been focused on adult cancers. Despite the advent of targeted therapies and immunotherapies, the treatment of childhood cancers relies largely on chemotherapy and radiation, both of which can create lifelong side effects in developing bodies. And cancer remains the leading cause of death by disease in children in the United States and the United Kingdom. C-Further, an international consortium created by LifeArc and Cancer Research Horizons, is working to advance innovative treatments for childhood cancers. It not only provides funding to discover and develop transformative therapies to treat childhood cancers but also leverages its network to help advance promising therapies. We spoke to David Jenkinson, head of childhood cancer translational challenge at LifeArc, about the approach C-Further is taking, the scientific and economic challenges of developing treatments for childhood cancers, and why new models for advancing these therapies are needed.

Avion was a healthy and athletic 15-year-old who became critically ill when he was admitted into a pediatric intensive care unit. For Robin Williams, assistant professor of pediatric hematology/oncology at the University of Minnesota Masonic Children's Hospital, Avion offered a medical puzzle she couldn’t crack on her own. His immune system was on overdrive and it was attacking healthy cells and organs within his body. Though testing ruled out blood cancers, it was only when Williams consulted a friend outside the hospital that she realized Avion was suffering from TAFRO, a subtype of the ultra-rare disorder idiopathic multicentric Castleman’s disease, a condition that has characteristics of both blood cancers and autoimmune disease. We spoke to Williams about the challenges physicians face in diagnosing patients with rare diseases, the thought process she went through in Avion’s case, and why she’s working to educate other physicians about the ultra-rare condition.

Recurrent respiratory papillomatosis is a potentially life-threatening disease of the upper and lower respiratory tract caused by chronic infection with human papillomavirus type 6 or type 11. In the absence of approved therapies, people with the condition often undergo repeated surgeries to clear their airways. The U.S. Food and Drug Administration in August approved Precigen’s Papzimeos, an immunotherapy that targets the underlying cause of the RRP, as the first approved therapy to treat the condition. We spoke to Kim McClellan, president of the Recurrent Respiratory Papillomatosis Foundation and Simon Best, associate professor of otolaryngology-head and new surgery at Johns Hopkins Medicine, about recurrent respiratory papillomatosis, the daily impact the condition can have on the lives of people with the disease, and what the approval of this therapy means for people living with the condition. 

Tris Dyson founded Challenge Works to incentivize innovators to solve societal problems. Dyson, who was diagnosed with amyotrophic lateral sclerosis, is now using the platform to find new treatments for the progressive neurodegenerative disease. The $10 million Challenge Works' Longitude Prize on ALS harnesses AI, open collaboration, and big data to find new treatments for the condition. We spoke to Dyson, managing director of Challenge Works, about his diagnosis of ALS, the case for using a prize to spur innovation, and the potential for leveraging AI to find treatments for the disease.