On Rare

In this episode of On Rare: Innovators, hosts David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Senior Director of Patient Advocacy at BridgeBio, speak with Kat Bryant Knudson, Founder and CEO of the Speak Foundation and a leader in the limb-girdle muscular dystrophy (LGMD) community. Diagnosed as a child after experiencing early symptoms of muscle breakdown, Kat spent years searching for answers before receiving a definitive genetic diagnosis. What began as a personal journey to understand her condition evolved into a lifelong commitment to ensuring that no one with LGMD faces that journey alone. From founding the Speak Foundation in an unexpected twist of fate to organizing groundbreaking scientific workshops that bring patients, researchers, industry, and the FDA to the same table, Kat has helped reshape how the LGMD community connects, advocates, and advances research. Guided by the belief that people with lived experience should have the loudest voice in the room, Kat continues to innovate on behalf of a diverse and growing rare disease community. Kat’s story is a reminder that progress begins with connection, shared experience, and the courage to speak up. Pantene is a third-party trademark. BridgeBio is not affiliated with or endorsed by Pantene or Procter & Gamble, and this reference is for storytelling purposes only.

En el episodio inaugural de On Rare: Innovadores, una nueva serie derivada de On Rare de BridgeBio, los presentadores David Rintell, director de abogacía de pacientes de BridgeBio, y Mandy Rohrig, directora sénior de abogacía de pacientes de BridgeBio, presentan a los oyentes a las personas que están transformando la comunidad de enfermedades raras a través de la defensa de los derechos, la compasión y la acción. La serie comienza en Gijón, España, con Carmen Alonso, fundadora de la Fundación ALPE, quien ha dedicado su vida a mejorar la atención y construir una comunidad para las personas y familias que viven con acondroplasia. Lo que comenzó como el viaje personal de Carmen, una madre que buscaba información y apoyo, se convirtió en una red internacional que ha transformado la comprensión y el manejo de la acondroplasia y otras displasias esqueléticas. Acompañada por su hijo Yago y su colega Fani, Carmen reflexiona sobre las lecciones de amor e inclusión que han guiado su trabajo y la convicción de que "siempre se puede hacer algo". A través de la historia de Carmen, On Rare: Innovators celebra a los líderes cuyas ideas y determinación impulsan el cambio en la ciencia, la defensa de los derechos y la comunidad. Su trabajo nos recuerda que la innovación no se encuentra solo en los laboratorios o las salas de juntas, sino que florece dondequiera que las personas decidan actuar con propósito y corazón.

Greg’s journey with LMNA cardiomyopathy, a rare inherited heart condition, began in high school when he experienced sudden episodes of rapid, irregular heartbeats during track practice. The cause remained a mystery for years, leading to misdiagnoses and untreated disease progression. During that time, Greg faced life-threatening arrhythmias and required several implanted devices before finally receiving a heart transplant. That experience, and the challenges that came before it, ultimately inspired his passion to create change and help others facing the same uncertainty. In this episode of On Rare, David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Senior Director of Patient Advocacy at BridgeBio, speak with Greg about the long road to diagnosis, the emotional impact of learning he had passed the condition on to his children, and his transformation into an advocate as president of the DCM Foundation. He also shares how his personal experience led to the launch of Everygene, a free genetic testing program for people with cardiomyopathies. Dr. Clayton Beard, Chief Scientific Officer at BridgeBio Gene Therapy, provides a high-level medical overview of LMNA-related dilated cardiomyopathy, a form of heart disease caused by mutations in the LMNA gene that compromise the structural integrity of heart cells and disrupt electrical signaling. He explains how these changes can cause dangerous arrhythmias, weaken the heart muscle, and lead to heart failure, making LMNA cardiomyopathy one of the most severe genetic forms of the condition. Dr. Beard also highlights the importance of early genetic testing for at-risk families, the role of research in improving detection and treatment, and how a better understanding of LMNA can lead to life-saving interventions.

Before she turned eight, Cerys had already faced two diagnoses, only one of which she truly understood. While being diagnosed with celiac disease as a child, unusually high CK levels in her blood pointed to a deeper issue: limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). In this episode of On Rare, David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Senior Director of Patient Advocacy at BridgeBio Gene Therapy, speak with Cerys, a 23-year-old living in Wales, about living with LGMD2I/R9. She shares how she’s navigated symptom progression, adapted to using mobility aids, and discovered the power of telling her story through her podcast, Unbalanced. When Cerys was first diagnosed with LGMD2I/R9 at age seven 7 years old, she didn’t fully understand the diagnosis. Her parents carried the emotional weight, trying to protect her from fear of what was ahead. It wasn’t until her muscle weakness became impossible to ignore, at 12 years old, that the condition began to define her daily life. From navigating stairs and driving to embracing a wheelchair, Cerys has had to adapt physically, emotionally, and socially, all while managing her energy levels so that she can continue to do the activities she loves. She finds strength in the LGMD community and hope in research, representation, and connection. In 2023, she launched Unbalanced to amplify stories like hers because growing up, she didn’t see anyone with a disability who looked like her. Now, she’s determined to be that voice for others. Dr. Anna Talaga, Director of Medical Affairs at ML Bio Solutions (a BridgeBio affiliate), provides a medical overview of LGMD. LGMDs are a group of genetic diseases that cause progressive muscle weakness and wasting, particularly in the shoulders, hips, and thighs. In some people, the heart and respiratory muscles may be impacted. Unlike many genetic conditions that are caused by a mutation in a single gene, LGMD can result from mutations in many different genes because they all affect the same protein complex that supports and stabilizes muscle fibers. LGMD type 2I/R9 (LGMD2I/R9), specifically, is caused by mutations in the FKRP gene, which is critical for maintaining muscle fiber integrity. Diagnosis typically begins with symptoms like difficulty walking, climbing stairs, or standing from a seated position, and is confirmed through genetic testing. LGMD2I/R9 is a progressive disease and there are currently no approved treatments that slow or stop its progression.

Katie and Allie’s story began in childhood with unexplained clumsiness and subtle symptoms that intensified over time. After years of searching for answers, Katie was diagnosed with late-onset Tay-Sachs (LOTS), a rare neurodegenerative disease. Further testing confirmed her twin sister Allie’s diagnosis as well. Despite facing daily challenges ranging from mobility issues to emotional strain, the sisters have become passionate advocates, raising over $1 million for research and awareness. With humor, grit, and the support of their family—especially their powerhouse mom—they continue to live fully and inspire the rare disease community. In this moving episode of On Rare, David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Senior Director of Patient Advocacy at BridgeBio Gene Therapy, speak with Katie and Allie, who share their experience with late-onset Tay-Sachs. The episode explores how Tay-Sachs, typically diagnosed in childhood, can present in adulthood, the emotional toll of navigating a progressive rare disease, and the resilience of a close-knit sibling duo who’ve turned advocacy into action. Diana Jussila, Director of Family Services at the National Tay-Sachs & Allied Diseases Association (NTSAD), provides essential insights into late-onset Tay-Sachs disease, a rare, progressive, neurodegenerative condition caused by mutations in the HEXA gene leading to deficiency of the Hex A enzyme. Without this enzyme, toxic substances accumulate in the brain and spinal cord, resulting in symptoms like muscle weakness, balance issues, speech difficulties, and psychiatric challenges. With no approved treatments and only supportive care available, community connection, advocacy, and ongoing research are vital lifelines for those living with late-onset Tay-Sachs disease.

When Julien was just 6 weeks old, Kady knew something wasn’t right. Despite more than 16 doctors insisting Julien was fine, Kady trusted her instincts and fought for answers—refusing to leave the hospital until the right tests were done. That persistence led to a life-changing diagnosis: a rare genetic form of hypoparathyroidism. Julien’s specific mutation is so unique that he is the only known case in the world. In today’s episode of On Rare, David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Director of Patient Advocacy at BridgeBio Gene Therapy, speak with Kady, the mother of Julien, a 4-year-old boy living with ADH1. Managing his condition has been a daily balancing act, as too little calcium leads to painful, debilitating symptoms, while too much threatens his kidneys. Kady shares the emotional journey of raising a child with a rare disease, from relentless advocacy to empowering Julien with the knowledge to recognize and communicate his own symptoms. Michael Collins, M.D., a research scientist at the National Institute of Health (NIH), provides a medical overview of Autosomal Dominant Hypocalcemia Type 1 (ADH1), a rare form of hypoparathyroidism that leads to low blood calcium levels. While most cases of hypoparathyroidism result from accidental gland removal during thyroid surgery, ADH1 is caused by genetic mutations. Often going undiagnosed until a child presents with severe symptoms, ADH1 is difficult to catch early since calcium levels are not part of routine pediatric screenings. The condition is also difficult to treat because standard calcium supplements, which alleviate ADH1 symptoms, can worsen kidney complications, increasing the risk of severe kidney stones and even renal failure. Treatment requires a delicate balance to avoid overcorrection and long-term kidney damage. Dr. Collins sheds light on the complexities of this condition and the challenges both patients and doctors face in managing it.

Charles, a recently retired cardiologist of 53 years, speaks with David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Director of Patient Advocacy at BridgeBio Gene Therapy, about how his unexpected early diagnosis of ATTR-CM likely impacted the trajectory of his disease. Dr. Jonathan Fox, President and Chief Medical Officer of cardiorenal programs at BridgeBio, explains how ATTR affects the heart and peripheral nervous system, and the importance of early diagnosis. For years, Charles suffered from numbness and tingling in both wrists and hands. Eventually, when the pain became so severe that operating a mouse for 10 to 15 minutes was difficult, he was referred to a hand surgeon who recommended carpal tunnel surgery. Preparing for the surgery, Charles recalled reading a medical journal article that indicated 10% of people who underwent carpel tunnel surgery had positive tissue biopsy indicative of ATTR-CM. He requested that his surgeon perform a biopsy and shortly thereafter received his diagnosis. The transition from doctor to patient was not easy for Charles. However, he feels fortunate to be a cardiologist, to have read and remembered the article, requested a biopsy, and received the diagnosis more quickly than many others who live with ATTR. “I have three passions: running, traveling, and teaching," Charles shared. The early diagnosis has allowed him to continue to live a full, active life, running nearly daily as he has for the past 45 years. Charles, now 86, continues to serve others, spending his retirement teaching and mentoring health care providers around the country about ATTR and volunteering for amyloidosis advocacy organizations.

In today’s episode of On Rare, David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Director of Patient Advocacy at BridgeBio Gene Therapy, speak with Misty about her experience living with limb-girdle muscular dystrophy, type2I/R9 (LGMD2I/R9). Misty details the suffering she experienced in her childhood from bullying for the symptoms she now realizes are connected to LGMD2I/R9 and shares the many frustrations and significant challenges that resulted from her delayed diagnosis. Despite noticing alarming symptoms as early as junior high school, Misty was dismissed by medical professionals for years. Finally, and only after both her younger twin sisters were diagnosed with LGMD2I/R9, Misty received her own genetic confirmation of LGMD2I/R9. She was 32 years old. Receiving her diagnosis was like an emotional tornado, and immediately, Misty feared that she may have passed LGMD2I/R9 on to her children. Throughout her journey, Misty has tried to hold on to the positives. She talks about the creative ways she has adapted to life with a progressive disease and emphasizes the importance of showing oneself grace and finding community. Ada Lee, M.D., Medical Director at ML Bio Solutions, a BridgeBio company developing BBP-418 for LGMD2I/R9, provides an overview of the genetic condition. She explains that limb-girdle muscular dystrophy (LGMD) is an umbrella of diseases associated with progressive muscular weakness in the girdle muscles, some of the central muscles that support limbs. LGMD2I/R9 (also called “LGMD R9 FKRP-related”) is a genetic disease caused by a mutation in the FKRP gene. The FKRP gene is involved in helping muscles build a glycoprotein called alpha-dystroglycan. When the gene doesn’t work correctly, it causes damage to muscle tissue, and over time, develops into scar-like, fibrotic tissue. As fibrotic tissue overtakes healthy muscle tissue, muscle strength and function declines, and people living with LGMD2I/R9 lose the ability to perform routine daily activities unassisted—such as walking or standing up. Many people with LGMD2I/R9 have prolonged pathways to diagnosis because it is a rare disease with an early onset of symptoms. To learn more about LGMD2I/R9 and the LGMD community, visit the LGMD Awareness Foundation, the CureLGMD2i Foundation, and The Speak Foundation.

Sean joins David Rintell, Head of Patient Advocacy at BridgeBio, and Mandy Rohrig, Director of Patient Advocacy at BridgeBio Gene Therapy to share his journey with ATTR. In this episode, Sean describes his initial symptoms, which included carpal tunnel syndrome and numbness in his foot and ankle, the misdiagnosis he experienced, and his eventual diagnosis at the Cleveland Clinic in Abu Dhabi. While the diagnosis was a relief it was also difficult to accept and took an emotional toll on him and those around him. Sean has found this to be a common experience of many diagnosed with ATTR. Since Sean’s form of ATTR is hereditary, various members of his family have also been tested. Sean also highlights the positive changes in his life, including meeting his wife, Robin, discovering a talent for drawing, and becoming a public speaker about ATTR. Jonathan Fox, President and Chief Medical Officer of cardiorenal programs at BridgeBio, joins us again to give a medical introduction to ATTR. On this episode, Jonathan highlights the differences of the ATTR T80 variant. Previously, we learned that ATTR amyloidosis is caused by the dissociation of a protein called transthyretin, or TTR, that changes its shape and forms into fibrous clumps. These clumps of misshapen protein are deposited into various organs and peripheral nerves, including the heart, which can cause them to function abnormally. Jonathan explains the possible origin of the T80 variant and how the T80 variant symptoms can differ from ATTR-CM. To learn more about living with amyloidosis visit Mackenzie's Mission, www.mm713.org

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Eric joins David Rintell, Head of Patient Advocacy at BridgeBio and Mandy Rohrig, Director of Patient Advocacy at BridgeBio Gene Therapy in a two-part conversation to talk about his experience of living with Transthyretin Amyloidosis (ATTR). Eric was an extremely active person who enjoyed sports, riding horses and working on his 20-acre property when he began to have issues which he now attributes to ATTR. Eric’s diagnostic journey took 14 years and as the disease progressed, he experienced two carpal tunnel surgeries, and several other cardiac procedures. In fact, by the time he was diagnosed, Eric could not walk the length of his home (60 feet) without getting out of breath. Four years after his diagnosis he received a heart transplant. Despite the difficulties, Eric highlights the positives of this diagnosis and how living with ATTR and engaging with the ATTR community has taught him to be intellectually curious, empathetic, grateful for the care he has received and happy to be alive. Jonathan Fox, President and Chief Medical Officer of cardiorenal programs at BridgeBio gives a medical introduction to ATTR-CM. Jonathan explains the causes of ATTR and what happens to people living with it. ATTR amyloidosis is caused by the dissociation of a protein called transthyretin, or TTR, that changes its shape and forms into fibrous clumps. These clumps of misshapen protein are deposited into various organs and peripheral nerves, including the heart, which can cause them to function abnormally.

Becoming a parent to a child with a rare disease was extremely isolating for Effie. In the second episode of our two-part series with Effie, she shares that finding the world of podcasts, documenting similar experiences to her own, was magical. Effie explains how important it is to find others who "get it" and how this feeling of belonging changed everything for her. As Effie explains, “In this community of rare disease families, every story matters, every effort counts, and every heart is connected. We are stronger together and are empowered by the love that guides us.” She describes her secret to conducting a compelling interview and reminds us to remember who we are here to serve – patients and caregivers. To learn more about Effie, her son Ford, his amazing laugh and CTNNB1 go back and listen to the first episode of the two-part series.