Genetic Mechanic: Stanley Crooke on Fixing Nano-Rare Disease with Oligos

Genetic Mechanic: Stanley Crooke on Fixing Nano-Rare Disease with Oligos

In this episode of Dose of Discovery, hosts Søren and AJ speak to physician-scientist Stanley Crooke, CEO of the nonprofit n-Lorem Foundation, about how antisense oligonucleotide (ASO) technology has evolved into a revolutionary therapeutic modality. Their conversation explores Stan's expansive career journey, from his early days building cancer programs at Bristol Labs and SmithKline to his bold decision to launch Ionis in 1989 when the industry doubted ASO technology. Stan discusses the emotional rollercoaster of biotech drug development, the inefficiencies of traditional small molecule discovery, and what led him to establish the n-Lorem Foundation. He shares how the regulatory frontiers of treating nano-rare genetic conditions “for free, for life” are changing rapidly and why innovations like patient-derived stem cells are driving drug development forward, one patient at a time. In this episode: * 03:41 – Explainer: What are ASOs? * 06:50 – Stanley Crooke’s journey and his journey into biomedicine * 10:31 – Frustrations with big pharma, founding Ionis * 15:05 – Trailblazing on ASO medicinal chemistry * 19:33 – Building company culture amid clinical failure * 22:56 – Spinraza (nusinersen) and the economics of drug pricing * 28:08 – Launching the n-Lorem Foundation for nano-rare diseases * 30:57 – “Free for life” ASO therapies * 36:55 – Impact on n-Lorem’s patients * 39:36 – “Everything we thought we knew about developmental delay is wrong.” * 34:58 – Redefining traditional diseases n-of-1 trial success * 26:12 – “Just tell me what the cause is. I'll fix it.” * 37:22 – 90% success rate for n-of-1 work * 45:08 – Moving beyond animal models with patient-derived iPSCs * 52:23 – Biology is shifting industry toward platforms * 55:55 – Wrap up and key takeaways About the guest Physician-scientist Stanley Crooke, founder of Ionis Pharmaceuticals, and founder, chairman, and CEO of the n-Lorem Foundation. Widely regarded as a pioneer of antisense medicine, he helped lead the development and commercialization of the first approved ASO therapies. Today, his work through nonprofit organization the n-Lorem Foundation focuses on creating and providing bespoke ASO treatments to patients suffering from nano-rare genetic conditions (affecting fewer than 30 people worldwide) for free, for life. Crooke studied pharmacy at Butler University and went on to earn his MD and PhD at Baylor College of Medicine. https://www.nlorem.org/wp-content/uploads/2023/08/Stanley-T.-Crooke-M.D.-Ph.D.-Bio.pdf [https://www.nlorem.org/wp-content/uploads/2023/08/Stanley-T.-Crooke-M.D.-Ph.D.-Bio.pdf] Dose of Discovery is cohosted by Søren Hough and Ayokunmi Ajetunmobi (AJ) and produced by Suze Cooper. LINKS: Kinds of KANDness: Battling nano-rare disease with oligos [https://www.bioxconomy.com/modalities/kinds-of-kandness-battling-nano-rare-disease-with-oligos] by Søren Hough Therapeutic oligos for no profit: A discussion with n-Lorem [https://www.bioxconomy.com/modalities/therapeutic-oligos-for-no-profit-a-discussion-with-n-lorem] by Søren Hough ‘For free, for life’: n-Lorem carves path for bespoke treatment [https://www.bioxconomy.com/modalities/-for-free-for-life-n-lorem-carves-path-for-bespoke-treatment] by Søren Hough Deep brain penetration by oligos enables Alzheimer’s, Parkinson’s treatment [https://www.bioxconomy.com/modalities/deep-brain-penetration-by-oligos-enables-alzheimer-s-parkinson-s-treatment] by Søren Hough (ASO treatment for neurodegeneration) Oligo-based therapies lead charge against prion disease [https://www.bioxconomy.com/modalities/oligo-based-therapies-lead-charge-against-prion-disease] by Nnenna Ohaka (Getting ASOs into the brain) Phosphorothioate antisense oligonucleotide induced innate immune activation is attenuated by tryptophan oxidation products [https://pubmed.ncbi.nlm.nih.gov/41978261/] (Making safe ASOs by Crooke and colleagues) Establishing a commercial solution for extremely rare genetic diseases [https://pubmed.ncbi.nlm.nih.gov/41772185/] (Commercializing ASOs for rare disease by Crooke & Lo) Read more at Bioxconomy [https://www.bioxconomy.com/modalities], sign up to our newsletter [https://get.informaconnect.com/tides-newsletter-signup/], and don’t forget to check out our upcoming events [https://www.bioxconomy.com/events]. You can find a fully annotated transcript of the episode here [https://www.bioxconomy.com/modalities/dose-of-discovery-stanley-crooke-on-fixing-nano-rare-disease-with-oligos]. ---------------------------------------- Hosted on Acast. See acast.com/privacy [https://acast.com/privacy] for more information.

Serendipity and siRNA: Julia Alterman on Expanding RNA Therapeutics

Welcome to Dose of Discovery: a dose of breakthrough medical discoveries, delivered with your morning coffee. (Coffee not included.) In this first episode, hosts AJ and Søren speak to Julia Alterman, assistant professor at the RNA Therapeutics Institute at UMass Chan Medical School, about how siRNA technology has evolved from a useful laboratory research tool into a promising therapeutic modality. Their conversation explores innovations in siRNA chemistry and how these changes have enabled researchers to craft potent siRNA drugs. Julia talks about her unlikely beginnings as a theater major before finding her way into biology – eventually leading her into the biotech industry and academia. Along the way, she discusses the challenges of delivering siRNAs beyond the liver into harder-to-reach tissues such as the brain and muscle, and the serendipitous discovery that helped launch Atalanta Therapeutics. In this episode: * 04:23 – Explainer: What are siRNAs? * 08:42 – Meet Julia Alterman * 12:39 – Julia’s history in industry * 16:33 – UMass and a PhD pivot * 18:28 – siRNAs versus ASOs * 21:39 – siRNAs versus CRISPR * 28:33 – A serendipitous breakthrough * 38:02 – Baby steps and big leaps * 42:10 – Stability and the therapeutic window * 46:27 – The importance of strong science communication * 50:55 – Scientists and VC funding * 54:28 – Wrap up and reflections About the guest Julia Alterman is an assistant professor at the RNA Therapeutics Institute at UMass Chan Medical School, where she develops new siRNA therapies for genetically defined diseases. Her work spans RNA chemistry, delivery, and pharmacology. Her earlier research into siRNA scaffold was licensed to Atalanta Therapeutics for the treatment of neurodegenerative disease. https://www.umassmed.edu/khvorovalab/People/faculty/Julia-Alterman/ [https://www.umassmed.edu/khvorovalab/People/faculty/Julia-Alterman/] Dose of Discovery is cohosted by Søren Hough and Ayokunmi Ajetunmobi (AJ) and produced by Suze Cooper. LINKS: RNA Fact Sheet [https://www.genome.gov/about-genomics/educational-resources/fact-sheets/ribonucleic-acid-fact-sheet] from the National Human Genome Research Institute BioXconomy’s coverage of the Alterman and Khvorova labs: "siRNA backbone modifications boost therapeutic potential, study finds" [https://www.bioxconomy.com/modalities/sirna-backbone-modifications-boost-therapeutic-potential-study-finds] by Nnenna Ohaka (Exploration of exNA) "Cutting-edge siRNA therapy improves ALS symptoms, survival in mice" [https://www.bioxconomy.com/modalities/cutting-edge-sirna-therapy-improves-als-symptoms-survival-in-mice] by Søren Hough (Exploration of divalent siRNAs) "Long-lasting siRNAs could help cancer patients and older people resist muscle loss" [https://www.bioxconomy.com/modalities/long-lasting-sirnas-could-help-cancer-patients-and-older-people-resist-muscle-loss] by Søren Hough (Including a photo of a Belgian blue cow [https://eu-images.contentstack.com/v3/assets/blt72fb3b8b4630b7db/blt99e2832e408ed902/698f594cacefb700089368d7/Belgian_Blue_2006_01_16_9.png?width=1280&auto=webp&quality=80&format=jpg&disable=upscale]) "Oligo-based therapies lead charge against prion disease" [https://www.bioxconomy.com/modalities/oligo-based-therapies-lead-charge-against-prion-disease] by Nnenna Ohaka Read more at Bioxconomy [https://www.bioxconomy.com/modalities], sign up to our newsletter [https://get.informaconnect.com/tides-newsletter-signup/], and don’t forget to check out our upcoming events [https://www.bioxconomy.com/events]. You can find a fully annotated transcript of the episode here [https://www.bioxconomy.com/modalities/dose-of-discovery-julia-alterman-on-expanding-rna-therapeutics]. ---------------------------------------- Hosted on Acast. See acast.com/privacy [https://acast.com/privacy] for more information.

Dose of Discovery - Trailer

Dose of Discovery is a monthly science podcast about the people, ideas, and challenges shaping modern biomedicine. Tune in as hosts Søren and AJ have thoughtful, accessible conversations with leading scientists about complex subjects, following emerging therapeutics as they move from research to real-world impact. Dose of Discovery — BioXconomy’s flagship podcast — is for biotech professionals, researchers, and curious listeners alike. Subscribe now for your regular dose of breakthrough medical discoveries delivered with your morning coffee. (Coffee not included). Read more at BioXconomy: https://bioxconomy.com/ [https://bioxconomy.com/] Check out our upcoming events: https://www.bioxconomy.com/events [https://www.bioxconomy.com/events] 7898c6b0-4922-11f1-be3b-27c072cdfbe0 ---------------------------------------- Hosted on Acast. See acast.com/privacy [https://acast.com/privacy] for more information.