Patient Empowerment Program: A Rare Disease Podcast

A nano rare diagnosis does not just affect one person. It reshapes an entire family. Realities of the Nano-rare takes you inside that experience. Hear directly from n-Lorem COO and nano rare mom Sarah Glass as she joins host Stan Crooke to share the day-to-day realities of raising her son Ethan and the ripple effects on their whole family, including his older sister. Discover how they have adapted, what they have learned, and how they have built a new normal. Tune in to this powerful two-part series featuring both Sarah and Oliver Glass. On This Episode We Discuss: 5:08 – Introduction to Sarah Glass and her family's Nano-rare experience 9:00 – Initial challenges of accurately identifying Sarah's son Ethan had a Nano-rare disease 11:30 – Symptoms and telltale signs that there was something else going on with Ethan 14:45 – Identifying that Ethan has DYRK1A 17:20 – Challenges of finding solutions post-diagnosis 20:20 – Navigating Sarah's son's DYRK1A with her unaffected daughter 23: 04 – What's a good day with DYRK1A? 27:01 – What's a bad day with DYRK1A? 34:30 – Managing frustrations of taking care of someone with a Nano-rare disease 37:05 – Compromises in professional life 41:00 – Planning for contingencies 43:10 – Unexpected tender moments of raising someone with DYRK1A 47:30 – Advice for managing expectations, future plans, and working with others Make sure to check out our sponsor Chemgenes!

On This episode We Discuss: 2:30 – Andrew realized that finance plays a very large role in drug development and is an obstacle in for rare disease patients getting the treatments they need 4:30 – The triple whammy of drug development 6:22 – Economic decisions when lives are at stake; Balancing the ethical considerations of medicine and finance 12:17 – Small biotech companies are better for innovation, and a distributed investment process is more productive; Innovation comes from orthogonal thinking 22:40 – Very small prevalence disease drug programs tend to get terminated at commercial organizations; Movement toward finding a way to create a commercial path for extremely rare disease drugs 25:45 – FDA draft guidance for potential commercialization of nano-rare medicines; Where the guidance may lead; Value of a statistical life 30:32 – The cost of a nano-rare patient’s care; Courageous moves of the FDA 35:00 – Regulatory processes merging with the advances of science while still protecting patients Andrew W. Lo is the Charles E. and Susan T. Harris Professor at the MIT Sloan School of Management, director of MIT’s Laboratory for Financial Engineering, and principal investigator at MIT’s Computer Science and Artificial Intelligence Laboratory. His healthcare-related research interests include: new financial engineering tools and business models for drug and device development and healthcare delivery, especially for rare and ultra-rare diseases; statistical methods for incorporating patient preferences into the drug approval process; predicting clinical trial outcomes via machine learning techniques; and novel reimbursement models for creating a robust gene and cell therapy ecosystem. He is a co-founder of BridgeBio Pharma, QLS Advisors, Quantile Health, and Uncommon Cures; a director of AbCellera, Atomwise, BridgeBio, Uncommon Cures, and Vesalius; and a member of the advisory board to the American Cancer Society’s BrightEdge Impact Fund. Lo received his B.A. in economics from Yale University and his A.M. and Ph.D. in economics from Harvard University. Patient Empowerment Program host: Stan Crooke, n-Lorem Founder and CEO

Today, we’re launching a NEW SERIES that pulls back the curtain on the scientific and medical breakthroughs that make n-Lorem possible. We call them miracles and without them, n-Lorem would not exist today. Every day, our patients benefit from what can only be described as miracles of science. Not the fairytale kind. Not wishes granted overnight. These miracles are earned by humans. Built over centuries by scientists whose discoveries stacked, evolved, and refined over time. They are the result of human curiosity, persistence, and an ever-deepening understanding of biology, and they’ve fundamentally changed how we see the world and treat disease. Today’s miracle: Genomics. Coming next: iPSCs, the RNA World, and Antisense Technology. The breakthroughs that pushed possibility even further. ------ The Patient Empowerment Program podcast is hosted by n-Lorem Founder and CEO, Stan Crooke. Dr. Crooke recently joined the advisory board of the CNBC Cures, an initiative bringing together families, doctors, investors and regulators with one goal in mind: helping to raise awareness of, and improve patient outcomes for, the 30 million Americans suffering from rare diseases. You can join the CNBC Cures Newsletter here: https://www.cnbc.com/cnbc-cures-newsletter/ Today's sponsor is ChemGenes: https://www.chemgenes.com/

In this special Best Of episode, we revisit some of the powerful moments from the 2025 Nano-Rare Patient Colloquium—an extraordinary gathering that brought together more than 875 patients, family members, scientists, physicians, advocates, and industry leaders from around the world, both in person and virtually. This episode highlights moving patient stories, thought-provoking scientific conversations, and community-led discussions that reflect the momentum building across the nano-rare space. Together, these voices showcase the growing impact of personalized experimental medicines and the shared determination to turn possibility into progress. From inspiration to action, this Best Of captures the heart of the Colloquium—and the collective commitment to creating a brighter future for individuals and families living with nano-rare diseases. Recap page: https://www.nlorem.org/nano-rare-patient-colloquium-2025/ Colloquium YouTube Playlist (alternative to recap page): https://youtube.com/playlist?list=PLrDVyc3t26FxvnqoiApY_Qw1_weTAQ4MS&si=EWBvQ0ZdDH-Rq1mJ

Meet Grace Hoyt — a bright, witty high schooler with a passion for singing, art, and romantasy audiobooks. Grace also happens to live with a rare disease (FLVCR1) that has left her legally blind, unable to feel pain, and unsteady on her feet. On her 13th birthday, Grace received a first-of-its-kind ASO medicine designed by n-Lorem to preserve her remaining vision. Today, she can still read snippets of her beloved “book children” — the physical versions of her favorite audiobooks — and, importantly, recognize and assess her sometimes life-threatening skin infections, a skill that could save her life.

The ‘Hero of n-Lorem’ Award is a recognition given to an individual volunteer or organization that has made substantial contributions to n-Lorem and our nano-rare patients. This honor recognizes our ‘unsung heroes’, those who have gone the extra mile, taken time away from their schedules and families and leveraged their expertise and contacts to support n-Lorem’s mission to provide hope and potential help to nano-rare patients. On this episode of the Patient Empowerment Program podcast, we welcome three of our five 2025 Heroes for a conversation about their inspiration to take action: - Wendy Erler, Senior Vice President, Patient Affairs, Sarepta Therapeutics - Richard S. Geary, Ph.D., Chief Development Officer, Executive Vice President of Development, Ionis Pharmaceuticals - Scott Henry, Ph.D., DABT, SVP, Nonclinical Development, Ionis Pharmaceuticals Sponsors: ChemGenes Hongene Biotech NRPC25: https://www.nlorem.org/nano-rare-patient-colloquium-2025/

Sarah and Ryan Marta, proud parents of three girls from Central Texas, began noticing that their middle daughter, Kinsley, was slow to reach mobility milestones in her early years. During a visit to a friend’s house, concerns about her vision were raised, prompting a check-up. What began as a single hospital visit quickly turned into many. An MRI revealed abnormal levels of white matter in Kinsley’s brain—leading to the devastating and confusing diagnosis of a nano-rare neurodegenerative disease called TUBB4A. Looking high and low for help, they eventually discovered n-Lorem, a non-profit that discovers and develops personalized medicines for extremely rare individuals like Kinsley. Kinsley is lively and cheerful with infectious laughter and a bright smile that lights up every room. She loves singing at the top of her lungs, swinging in the fresh air, and spending endless hours playing with her sisters and cousins. Kinsley uses a mobility walker to get around, but one of her biggest dreams is to run. When asked what she’d do after running, she simply says, “I’d run some more.” On This Episode We Discuss: 2:35 - Early signs of Kinsley’s disease and her TUBB4A diagnosis 4:00 - Fight or flight – Sarah and Ryan did all they could to seek help 7:30 - Defining TUBB4A 9:40 - Kinsley's challenges today 11:00 - The impact rare diseases have on families 14:40 – Kinsley wants to do more, and an n-Lorem medicine provides optimism Links: 2025 Nano-rare Patient Colloquium Agenda and Registration - https://www.nlorem.org/nano-rare-patient-colloquium-2025/ Donate to n-Lorem - https://www.nlorem.org/donate/ Hongene Biotech - https://hongene.com/

At n-Lorem, every investment decision carries real weight by directly affecting the nano-rare patients we serve. We think very deeply about each decision of how to invest the limited and precious dollars that we have. But what about investing in basic research to advance antisense oligonucleotide (ASO) technology for the future? Certainly, most of the money should and is being put towards creating ASOs to help patients in need today. Meanwhile, it is also our belief that we must invest to continue innovating and, in this episode, we explore the research occurring at n-Lorem today that will lead to better treatments for more nano-rare patients tomorrow. On this episode we discuss: - ASO technology is still evolving unlike other validated drug discovery technologies - Nano-rare patients need more from ASO technology - Reasons n-Lorem are unable to help more patients Loss of function mutations Mutations that cause dysfunction of an organ to which ASOs distribute at only high doses Innate immune activation Challenges in creating allele-selective ASOs - Solutions to these challenges are possible and we know how to do it Advances in loss of function mutations Targeted delivery to muscle, the immune system, the gut and heart Controlling innate immune activation Enhanced allele-selectivity Links: Colloquium - https://www.nlorem.org/nano-rare-patient-colloquium-2025/ Donate - https://www.nlorem.org/donate/

Connor Gooley is the first patient ever treated with an ASO for TUBB4A-Related Leukodystrophy, a condition that severely disrupts his nervous system, slows nerve impulses, and impairs his fine motor skills. As a result, Connor cannot speak, walk, sit up on his own, or chew well. Still, he manages to army crawl, propel himself in his wheelchair, and use a gait trainer. He’s also remarkably resilient—rarely crying or complaining despite the daily challenges he faces. In this episode of the Patient Empowerment Program, Connor’s parents, Diana and Mike, share their family’s journey from diagnosis to treatment and reflect on their observations of Connor after more than six months on an n-Lorem discovered and developed treatment. On This Episode We Discuss: 1:33 Shaking eyes were the first sign of Connor’s rare disease 4:10 An MRI revealed little to no myelin, leading to whole genome sequencing and an eventual TUBB4A genetic mutation diagnosis 7:10 Connecting with another family with the same mutation 10:00 Finding n-Lorem through a ‘seeking patient candidates’ advertisement in a Global Genes annual report 12:26 Contextualizing Connor’s TUBB4A mutation in simple terms 21:19 How rare diseases affect families and creating a new normal 27:41 Receiving treatment in Boston and contemplating the decision to agree to an experimental treatment for their son 32:00 Observations after 6 months on treatment 35:45 n-Lorem has given the Gooley family hope for a better future for Connor Links: Hongene Biotech: https://www.hongene.com/ Donate to n-Lorem / Support nano-rare: https://www.nlorem.org/donate/ n-Lorem 2025 NRPC: https://www.nlorem.org/nano-rare-patient-colloquium-2025/

What Are Chemicals? | How Drugs Work in the Body | Understanding Homeostasis We’re all made of chemicals—but what exactly is a chemical? In this video, we break down the basics: chemicals are forms of matter that exist as solids, liquids, or gases. Inside living organisms, these chemicals create complex networks that keep us alive and balanced—a process known as homeostasis. Drugs are chemicals too! They work by interacting with these biological networks to help restore or adjust how the body functions. Whether you’re a curious learner, a patient, or a future scientist, understanding these fundamentals can empower better decisions about your health and treatment. 🔬 Learn more about biology, medicine, and how science impacts your daily life. 💊 Subscribe for more videos on drug development, health, and patient education. Full Intro to Medical Science Playlist: https://www.youtube.com/playlist?list=PLrDVyc3t26Fy5aQpo3mulackGlUwrIqYL In This Episode, We Explore - What exactly is a chemical—and why it matters - The definition of a drug and how it works in the body - How chemical reactions power life - Biochemicals: the molecules that make living systems tick - Cells: the basic building blocks of life - Types of polymers and their roles in biology - The languages of life: how nucleic acids and proteins communicate - DNA and RNA—what they are and what they do - What happens when genes change: understanding mutations - The difference between helpful and harmful gene mutations

Connor Dalby was born with an SCN2A ion channel mutation causing severe epilepsy and eventually leading to hospice care at an early age. It was a chance hallway conversation between Connor’s mom and Dr. Stan Crooke at a conference that sparked the idea for what would become n-Lorem. In a full-circle moment, Connor went on to become the very first patient applied to and accepted by the foundation, giving him the designation 'Patient #001'. In March 2024, Connor received his personalized ASO medicine, and while Dr. Olivia Kim-McManus of Rady Children’s Hospital continues to fine-tune the optimal dose and schedule for the best and longest-lasting effects, Connor has, for the first time, taken steps on his own and experienced periods without seizures. Discover all of what has been observed in Connor since being treated in this episode of the Patient Empowerment Program podcast! This episode is brought to you by Hongene Biotech! On this episode we discuss: 2:45 – What Connor’s life was like from birth 4:20 – Finding a SCN2A diagnosis through genomic sequencing 6:40 – A hallway conversation between Kelley and Stan about Connor sparked the idea of the n-Lorem Foundation 9:20 – Dr. Olivia Kim-McManus on engaging and gaining institutional support to treat n-of-1 11:40 – Connor's program was uniquely challenging 14:18 – Connor unknowingly had coronavirus upon receiving his first ASO dose 18:00 – Symptoms that affect Connor’s life on a daily basis 18:55 – Connor has walked unassisted for the first time in his life 26:10 – Finding the optimal treatment dose and schedule 29:05 – Improvement of painful gastrointestinal (GI) issues Bios: Kelley Dalby is the Director of Natural History and Diagnostics in Epilepsy at Praxis Precision Medicines, where she has worked for four years. Kelley worked as a high school English teacher in San Diego until her son Connor was born with a severe form of epilepsy caused by a mutation in the SCN2A gene. When he was diagnosed, she co-founded a biotechnology company, RogCon, focused on discovering therapies for SCN2A mutations. Kelley served as Vice President and contributed to the companies’ success, including licensing the primary program to Praxis Precision Medicines. Dr. Olivia Kim-McManus is an Associate Clinical Professor, UC San Diego School of Medicine Dept of Neurosciences, Pediatric Neurologist and Epileptologist, Rady Children’s Hospital Precision Therapeutics Neuro-Interventional Program Director. She received her undergraduate degree in Neurosciences at Columbia University in New York City and medical degree at George Washington University Children’s National Medical Center. She specializes in treating children with medically intractable epilepsy due to rare genetic etiologies requiring targeted genetic therapies or epilepsy surgery. She is the Director of the Batten’s Disease Neuro-infusion Program at Rady Children’s Hospital where she delivers intraventricular cerliponase-alfa enzyme replacement therapy via Ommaya reservoir targeted for disease modifying therapy for rare pediatric genetic disease. Dr. Kim-McManus is Neurology Section Vice Chief of Medical Staff Executive Committee at Rady Children’s Hospital, ACGME Epilepsy Fellowship Associate Program Director at UCSD, Epilepsy Foundation San Diego Professional Advisory Board member, Rady Children’s Insitute for Genomic Medicine clinical investigator, and UCSD Altman Clinical and Translational Research Institute Scientific Review Board member. Links: n-Lorem Candle and Card Fundraiser - https://www.nlorem.org/mothers-day-candle-2025/ Hongene - https://www.hongene.com/

Our bodies are like bustling cities of cells, always chatting and working together. They don’t just send long-distance messages to organs—they also gossip locally, getting nearby cells to spring into action. Juxtacrine communication is like a handshake between cells—they have to be up close and personal to pass the message along! Unlike long-distance cellular calls, juxtacrine signaling requires direct contact, where one cell’s surface proteins interact with another’s, triggering a response. This episode is brought to you by Hongene Biotech who is continuously innovating to make RNA medicines accessible and affordable to patients worldwide. Visit www.hongene.com On this episode we discuss: Paracrine communication Recently found exosomes Cell to cell contact-dependent communication (Juxtacrine signaling) Tunneling microtubes Cell communication conclusions