Cardiovascular System Part 4B: (The Spigot) Kidney Diseases

What makes antisense oligonucleotides (ASOs) so special? Let’s first understand what an oligonucleotide is. An oligonucleotide is a short strand of synthetic DNA or RNA (a nucleic-acid chain), usually consisting of up to approximately 20 nucleotides long—designed to bind with specific sequences in the body. At n-Lorem, our ASO technology is built on more than 30 years of research, innovation, and investment. It’s uniquely suited for treating nano-rare diseases—ultra-rare genetic conditions that affect just one or a few individuals. The versatility and specificity of ASOs allow us to address a wide variety of gene mutations, creating customized therapies for each unique patient. Compared to other traditional drug discovery platforms, discovering and developing an optimal ASO is inexpensive, quick and can be used to treat diseases that are caused by many different types of gene mutations. ASOs work by binding to RNA, thereby modifying the expression of disease-causing proteins. This makes them exceptionally well-suited for treating diseases caused by rare or unique genetic mutations. On This Episode We Discuss: - The repurposing of small molecule drugs - The promise and limitations of gene replacement therapies - What makes ASO drug development different—and better—for nano-rare diseases - A brief history of modern drug development - How regulatory frameworks evolved after medical disasters - The decentralization of the biotechnology industry - What challenges still lie ahead in genetic medicine     Intro to Medical Science Series YouTube Playlist: https://www.youtube.com/playlist?list=PLrDVyc3t26Fy5aQpo3mulackGlUwrIqYL 

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/ 

For n-Lorem's Chief Operating Officer, Sarah Glass, the mission of n-Lorem is deeply personal. Her son Ethan was diagnosed with a nano-rare mutation, a journey that has shaped her commitment to the cause. A geneticist by training, Sarah joined n-Lorem to help lead and guide the organization in its efforts to offer hope and potential help through treatment opportunities to nano-rare patients and their families. This is more than just a job for her—she is driven by her love for her son and a passion to serve the entire nano-rare community. This episode is proudly sponsored by Hongene Biotech. “We are changing the landscape of rare disease drug discovery and development – starting with the most rare.” – Sarah Glass, Ph.D.   On This Episode We Discuss: ✔️ Sarah’s background in science and her early interests ✔️ How working at a Contract Research Organization (CRO) shaped her understanding of the patient experience ✔️ The challenges of rare disease clinical trials and why they are still relatively new ✔️ Sarah’s son, Ethan, and his journey as a nano-rare patient ✔️ How long it took for Ethan to receive a diagnosis and the symptoms he faces ✔️ How Sarah discovered n-Lorem, a nonprofit providing free, lifetime treatment for nano-rare patients ✔️ The emotional journey of caring for a nano-rare child—how parents navigate hope and uncertainty ✔️ What Sarah has learned while working at n-Lorem ✔️ The biggest surprises in her journey as both a mother and a scientist   If you’re passionate about rare diseases, personalized medicine, and patient advocacy, this episode is a must-watch! 💙 🔔 Subscribe for more stories from the rare disease community! #RareDisease #NanoRare #nLorem #PatientAdvocacy #geneticdisorders   Donate to n-Lorem: www.nlorem.org/donate  More about Hongene: 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

How do cells communicate with each other? With trillions of cells in the human body, seamless collaboration is essential within this intricate cellular society. Cells work together to form organs, and when one organ needs another to perform a task, they send signals across distances—much like picking up the phone and calling someone. Organ Hotline 📞 Eyes: Hey, Brain? This is Eyes. We’re reading this post about how organs communicate, and it’s really interesting. 📞 Brain: Oh, show me more! What’s it say? 📞 Eyes: Apparently, organs send signals to each other to get stuff done. Like, the liver calls the stomach when it’s time to detox! 📞 Brain: Whoa, I had no idea they were so organized! Keep reading, I need all the details! 📞 Eyes: I’m on it! But it says they made a whole podcast episode on in. 📞 Brain: Alright, I’m sold! I'm signaling to press play. On This Episode We Discuss: How cells talk to each other Multicellular organisms Why cells create organs Organ to organ communication - Electrochemical Chemical signals - The endocrine system Hormones created by other organs This episode is brought to you by Hongene Biotech: https://www.hongene.com/ Support n-Lorem and nano-rare patient: https://www.nlorem.org/donate/  

Rosie was the first of three HNRNPH2 patients to receive treatment with an n-Lorem ASO, helping to pave the way for others. Her parents, Nicole and Bobby, share their daughter's journey and how they have adapted as a family to meet her unique needs. As a pediatrician, Nicole understands the complexities of medical care, yet she acknowledges that even she doesn’t always have the answers when it comes to raising a child with a nano-rare disease—a reality that resonates with many nano-rare families. On this episode we discuss: 2:00 Bobby left his job to help care for Rosie full-time 7:36 Nicole is a pediatrician and it’s difficult for her to not regularly attend Rosie’s appointments 11:16 Rosie’s diagnosis of HNRNPH2 16:00 Even as a pediatrician, Nicole finds nano-rare diseases complex and difficult to navigate 19:29 What is HNRNPH2? 26:40 Coming to terms with the diagnosis 29:35 Weighing the potential risk/benefit and making the decision that Rosie will be the first HNRNPH2 patient treated with an experimental medicine 37:05 How Rosie is doing after three ASO treatment doses 40:35 Potential for a placebo effect and allowing multiple observers to notice changes   Donate to n-Lorem: https://www.nlorem.org/donate/ This episode is brought to you by Hongene Biotech: https://www.hongene.com/ 

Sloane was born with a KIF1A mutation and is a special case at n-Lorem—she was the first patient to receive a medicine originally designed for someone else. Her mother, Megan, and grandfather, Tom, join the Patient Empowerment Program to share her journey and provide an update on how she’s doing six months after treatment.  On This Episode We Discuss: Sloane’s KIF1A diagnosis  Nano-rare diseases affect the entire family Sloane was able to use the same ASO as another KIF1A patient Finding n-Lorem through KIF1A.ORG Shocked that n-Lorem was able to create personalized treatments efficiently at cost Sloane’s case is unique in a variety of ways and the decision to treat  How Sloane has responded to treatment Are better measurements of benefit needed for nano-rare patients? How Sloane has brought empathy, joy, and positivity to her family  Tom unretired to help fund research and support  The origins of ASO medicine is a long haul    Thank you to Hongene Biotech for sponsoring this patient story episode!   Make Hope Possible for nano-rare patients with a donation to n-Lorem.

Five years of creating medicines, instilling hope, and overcoming steep challenges—all with the singular goal of improving the lives of nano-rare disease patients. Along the way, we’ve proven that WE CAN treat these patients safely and effectively, delivering significant benefit. But what else have we discovered throughout this journey?  Thank you to Hongene Biotech Corporation for sponsoring this 5-Year Anniversary episode.  On This Episode We Discuss: - We CAN do this - n-Lorem is proof of the value of investing in science - We can treat nano-rare patients safely - The nano-rare patient population is large - We must introduce genomic sequencing into newborn evaluation - Most nano-rare diseases are more prevalent than we think - Most diseases are a composite of multiple mutations in one or more genes - A non-profit model in which patients are treated irrespective of their financial status is feasible - Nano-rare mutations are spread throughout the genome - Nano-rare mutations can affect any organ - Essentially all types of mutations can cause nano-rare diseases - Most nano-rare patients express severe, chronic, debilitating, progressive diseases - The journey to diagnosis is often unique, long, and perilous - Significant benefit can be achieved - ASOs administrated intrathecally for CNS diseases can result in profound benefit - ASOs can result in durable benefit - Many patients require allele-selective ASOs - The community is strong - Industrialized processes created by n-Lorem is delivering great value - The modified cross-over clinical design created by n-Lorem is delivering high quality data - If we raise the funds, we can meet the demand Donate: www.nlorem.org/donate 

Walt Whitman’s 1855 poem, I Sing the Body Electric, is a celebration of the human body and its intrinsic connection to the universe. During that era, scientists were just beginning to understand that humans are, indeed, electrical beings. Whitman’s deliberate use of the word "electric" in his tribute to the human body was quite remarkable, as the term was not widely used at the time and electricity for human use was still in the experimental stage. With that in mind, the poem’s title serves as both a poetic and scientific statement. Many have compared great science to art, but we believe it is more akin to poetry. A poet distills intricate concepts, stories, and emotions into the most concise, impactful expression—cutting through the noise to reach the heart and soul of the matter. Similarly, great scientists achieve this with their work. Together, scientists and patients contribute their own verses to the epic poem of understanding known as science. This episode of the Patient Empowerment Program podcast is proudly sponsored by Hongene Biotech. With more than 26 years of experience in the nucleic acid industry, Hongene is a specialized CDMO and raw materials supplier committed to providing high-quality and high value products and services with the best in class lead times. Make Hope Possible and donate, today www.nlorem.org/donate Episode sponsor: Hongene Biotech https://www.hongene.com/  

Join Stan Crooke, n-Lorem founder, CEO, and host of the Patient Empowerment Program Podcast, alongside Amy Williford, Sr. Director of Communications and Donor Relations, for a special episode. In this post-colloquium Q&A, Stan recaps the 2024 Nano-rare Patient Colloquium and the progress n-Lorem has made as the organization nears its 5-year anniversary, shares his candid reflections on the event, and dives into additional thoughts and questions that weren’t covered. Do you have additional questions? Email [email protected].   Question Bank: 2:15 How do you think the event went this year? 6:05 Were observations of benefit expected in patients so quickly?  9:47 What do you expect the number of patients treated to be next year? 10:57 Do you have a message to supporters? 12:30 Were there any disappointments from the colloquium? 13:21 What are the most important things that n-Lorem has learned this year?  16:13 Do you think n-Lorem’s processes will be outlined every year at the event? 18:05 How is AI incorporated at n-Lorem? 19:10 Does your recently announced deal with GondolaBio reflect the sustainability strategy discussed at the event? 20:53 n-Lorem is celebrating 5 years in 2025. Did you expect the foundation to be where it is today? 21:28 Does n-Lorem plan to expand into Europe and elsewhere?   Make hope possible with a donation.