'This Isn't Normal, And It Isn't Pain-Free': Luke Rosen's Parenting Journey

The Path from CNBC Cures: A Deep Dive into SYNGAP1 and Nano-Rare Diseases

Key Concepts:

• SYNGAP1: A neurodevelopmental disorder causing autism and intellectual disability, often impacting communication.
• KIF1A: A gene crucial for neuronal growth and health; mutations in this gene lead to a range of neurological disorders.
• Nano-Rare Diseases: Genetic diseases affecting fewer than 30 individuals globally, presenting unique challenges for research and treatment.
• Antisense Oligonucleotide (ASO) Therapy: A pioneering technique using synthetic DNA/RNA strands to correct disease-causing protein levels.
• Toxic Gain-of-Function Mutation: A genetic mutation that results in a protein with a new, harmful function.
• Catatonia: A state of unresponsiveness and immobility, sometimes mistaken for seizures.

I. Introduction & The Power of Shared Stories

The podcast episode, “The Path from CNBC Cures,” hosted by Becky Quick, centers on the personal journey of families navigating rare genetic diseases, specifically SYNGAP1 and KIF1A-related disorders. Quick emphasizes the importance of community and sharing experiences, noting the overwhelming response to the first episode – thousands of emails, texts, calls, and social media comments from individuals facing similar challenges. A dedicated email address, cnbc.cures@cnbc.com, has been established to facilitate continued conversation and support. The series is framed as “The Path” to reflect the repetitive, reinventive, and recommitting nature of life with rare disease.

II. The Rosen Family & The KIF1A.org Foundation

Luke Rosen, a former actor and current New York City firefighter, shares his family’s story. His daughter, Susannah, was diagnosed with a KIF1A mutation at two-and-a-half years old. The initial realization of a problem arose when Susannah couldn’t kick her legs during bath time, revealing an ataxic gait and eventual loss of walking ability. KIF1A, Rosen explains, is a molecular motor protein vital for brain function. Susannah’s mutation is a “toxic gain-of-function” mutation, meaning the altered protein actively damages neurons.

Driven by the lack of treatment options, Rosen and his wife, Sally, founded KIF1A.org. Rosen details the emotional toll of the diagnosis and the struggle to balance protecting their daughter’s privacy with the need to raise awareness and seek solutions. He highlights the isolation experienced by families facing rare diseases and the importance of finding a “tribe” for support. The Rosen’s journey involved navigating a complex medical landscape and ultimately advocating for research and treatment development.

III. The Science of Antisense Oligonucleotide (ASO) Therapy & N Lorem

The episode introduces Dr. Stanley Crooke, founder of Ionis Pharmaceuticals and N Lorem, a non-profit foundation focused on nano-rare diseases. Crooke explains the concept of nano-rare diseases – those affecting fewer than 30 people worldwide – and the challenges they present. He details the development of Antisense Oligonucleotide (ASO) therapy, a technique using short synthetic strands of genetic code to modify protein production.

Crooke recounts a pivotal moment when he was approached by parents of children with SCN2A mutations, a condition also treatable with ASO therapy. Despite initial commercial viability concerns, he realized the potential of the technology to help individual patients. This led to the founding of N Lorem, dedicated to developing treatments for these ultra-rare conditions. He clarifies that ASO therapy aims to correct protein levels – either increasing production when too little exists (like in Kaylie’s SYNGAP1 case) or decreasing it when there’s an excess.

IV. Susannah’s ASO Therapy Journey & Observable Improvements

Rosen details Susannah’s experience with ASO therapy, which took approximately two years from acceptance into the program to the first dose. He describes the emotional weight of the process, including anxieties about anesthesia and the desire to shield his daughter from fear.

Significant improvements were observed after the second dose. Rosen recounts a shift in their family breakfast dynamic, noting a reduction in Susannah’s tremors and increased energy levels. While acknowledging that a cure remains elusive, he emphasizes the tangible benefits of the therapy, including reduced pain, improved school attendance, and the ability to participate in activities like singing the National Anthem. He notes that while measurable outcomes like walking distance haven’t significantly changed, the quality of life improvements are profound. The Rosen’s also experienced a shift from seizures to catatonic episodes, highlighting the ongoing diagnostic challenges.

V. The Impact on Family Dynamics & The Need for Support

The episode candidly addresses the strain rare diseases place on families. Rosen reveals that he and his wife rarely sleep in the same bed due to the constant need for overnight care for Susannah. He cites a statistic indicating that 80% of marriages fail within the rare disease community, emphasizing the immense pressure and the need for proactive strategies to maintain a healthy relationship. The Rosen’s schedule intimacy on their Google Calendar as a testament to this challenge.

Quick shares her own experience, highlighting the importance of a supportive partner and the struggle to balance caregiving with personal needs. Both Quick and Rosen emphasize the privilege of having resources and access to information, and the need to support families who lack these advantages.

VI. Conclusion & Call to Action

The episode concludes with a powerful message of hope and resilience. Rosen emphasizes the purity and unwavering love of children like Susannah, despite the challenges they face. Quick reiterates the mission of CNBC Cures – to build a community, raise awareness, and accelerate research for rare diseases.

Listeners are encouraged to subscribe to the CNBC Cures newsletter, attend the upcoming summit, and share their stories. The episode serves as a poignant reminder of the human cost of rare diseases and the urgent need for continued innovation and support.

Notable Quotes:

• Luke Rosen: “This isn't normal and this isn't pain-free.”
• Dr. Stanley Crooke: “There is no solution for [nano-rare patients] other than what we can offer.”
• Becky Quick: “You have to stop thinking about what anybody thought of you, and I had to go ask everybody for help.”
• Luke Rosen: “It's making her life better. She's still not going to get up and run a marathon or speak in a full sentence, or she does. Her speech got much better, actually.”

Data & Statistics:

• Approximately millions of Americans have rare genetic diseases.
• Nano-rare diseases affect fewer than 30 individuals globally.
• 80% of marriages fail in the rare disease community.
• The FDA defines a rare disease as affecting a population of 200,000 or less.