6:52 – Experimental ASO treatments for genetic forms of ALS

9:30 – The creation of Silence ALS to treat extremely rare forms of genetically caused ALS like CHCHD10 and TARDBP and moving the collaboration forward

12:36 – Serving present day and future patient populations with the Silence ALS initiative

17:30 – Learnings gained from treated nano-rare ALS patients may translate to broader ALS groups

22:33 – To ALS patients and families, hope is powerful and makes a difference

Links:  Donate - https://www.nlorem.org/donate/  NRCP26 - https://www.nlorem.org/nano-rare-patient-colloquium-2026/  Hongene - https://www.hongene.com/ 

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.

This series has pulled back the curtain on the scientific and medical breakthroughs that make n-Lorem possible, including Genomic, Stem Cells, the RNA World and Antisense Technology. Their importance is consequential, and without these breakthroughs, n-Lorem would not exist today.

On this episode we discuss:

- The Evolution of the Drug Discovery and Development Industry

- The Rise of Small-Molecule Drug Discovery

- New Platforms That Expanded the Possibilities of Drug Discovery

- Why Antisense?

- How Ionis Created ASO Technology

Links:

Nano-rare Patient Colloquium 2026: https://www.nlorem.org/nano-rare-patient-colloquium-2026/ 

Support n-Lorem: https://www.nlorem.org/donate/ 

Episode sponsors:

Hongene: https://www.hongene.com/ 

Chemgenes: https://www.chemgenes.com/ 

Sign up for the CNBC Cures Newsletter: https://www.cnbc.com/cnbc-cures-newsletter/ 

On this episode we discuss:

1:25 – Celebrating 100 episodes of the n-Lorem Patient Empowerment Program podcast

6:40 – Welcome Becky Quick; CNBC Anchor and mother of a Kaylie

10:35 – Becky’s journalistic origins and path

16:13 – Launching CNBC Cures and the need to help others facing rare diseases

23:00 – Navigating life with the challenges caused by rare disease

29:03 – Kaylie’s SYNGAP1 diagnostic odyssey

42:10 – Tending with the loss of control

43:56 – Non-verbal does not mean lacking understanding

48:30 – SYNGAP1 explained

59:01 – Hope is powerful

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Make hope possible with a donation in support of nano-rare patient programs: https://www.nlorem.org/donate/ 

This episode is made possible thanks to our sponsors: Learn more about Chemgenes - https://www.chemgenes.com/ 

On this episode we discuss:

• 00:00 Introduction
• 00:58 Meet Bill O’Sullivan and Dr. Neil Shneider
• 03:17 Family history and inherited ALS
• 06:37 Diagnosis and discovery of CHCHD10
• 10:02 Early symptoms and diagnostic challenges
• 20:20 Beginning personalized ASO treatment
• 22:33 Treatment results and disease stabilization
• 23:42 Looking ahead: earlier intervention and future generations
• 27:57 Expanding treatment opportunities through genetic research

Links:

This episode is made possible thanks to our sponsor ChemGenes

Donate to n-Lorem and Make Hope Possible

Register to attend the 2026 Nano-rare Patient Colloquium

• 0:00 – Introduction to the mission of n-Lorem and hope for nano-rare patients and families.  
• 0:51 – Stan Crooke introduces the podcast and explains n-Lorem’s groundbreaking treatment model.  
• 1:12 – Overview of the RNA world and why different RNA types are essential to biology.  
• 1:48 – Introduction to translational RNAs and their role in making proteins.  
• 2:16 – Explanation of ribosomes and how they translate genetic code into proteins.  
• 5:12 – Discussion of pre-ribosomal RNA processing and the role of the nucleolus.  
• 7:48 – Ribosomes are compared to the Enigma machine for decoding biological information.  
• 9:29 – Overview of transfer RNAs (tRNAs), codons, and amino acid delivery.  
• 12:23 – Why decoding the genetic code was a landmark scientific breakthrough.  
• 14:18 – How tRNAs mature through RNA processing and splicing mechanisms.  
• 16:03 – Summary of how mRNA, rRNA, and tRNA work together during translation.  
• 18:37 – Introduction to processing RNAs and spliceosome machinery.  
• 21:15 – Explanation of U4 RNA and its role in RNA quality control and disease.  
• 23:00 – Overview of snoRNAs and their role in ribosomal RNA maturation.  
• 24:06 – Discussion of Cajal body RNAs and RNA modification systems.  
• 25:01 – Introduction to regulatory non-coding RNAs and antisense RNAs.  
• 27:50 – Overview of circular RNAs and their potential regulatory functions.  
• 28:51 – Explanation of microRNAs and how they regulate protein production.  
• 29:59 – Closing thoughts on regulatory RNAs and cellular control systems. 

• Shownotes:  
• 0:00 — Introduction to n-Lorem Overview of the n-Lorem Foundation mission and support for nano-rare patients and families. 
• 0:15 — Podcast & Sponsor Introduction Dr. Stan Crooke introduces the podcast and acknowledges sponsor ChemGenes. 
• 1:17 — Entering the “RNA World” Dr. Crooke introduces RNA biology and explains why RNA science is foundational to antisense therapies. 
• 1:31 — What Are Pre-RNAs? Explanation of immature “pre-RNAs” and how they contain instructions for cellular processing and transport. 
• 3:31 — RNA Processing & Adding Nucleotides Discussion of how RNAs are trimmed and modified during maturation. 
• 4:03 — Poly-A Tails Explained What poly-A tails are, why they are added to messenger RNA, and how they protect RNA molecules. 
• 7:07 — Protecting RNA from Degradation How cells chemically protect both ends of RNA molecules. 
• 9:00 — The 5’ Cap Introduction to RNA “caps” and their role in identifying and stabilizing messenger RNA. 
• 11:02 — RNA Splicing How cells remove unnecessary RNA segments (introns) and reconnect useful coding regions. 
• 14:06 — RNA Structural Codes How RNA folds into structures and why shape is important for function. 
• 16:09 — Chemical Modification Codes Overview of RNA chemical modifications and how they add another layer of cellular regulation. 
• 18:22 — RNA as Cellular Management Dr. Crooke compares RNA molecules to executives and middle managers directing cellular operations. 
• 19:12 — RNA & Antisense Technology Why understanding RNA biology is critical for developing antisense therapies for nano-rare diseases. 
• 22:08 — DNA vs. RNA Analogy DNA as the “king” and RNA as the active workforce managing the affairs of the cell. 
• 24:10 — The Dynamic Nature of RNA How RNA constantly changes structure, interactions, and function over time. 
• 26:14 — Closing Thoughts Final overview of RNA versatility and its role in cellular communication and regulation. 
• 26:54 — About n-Lorem Information about n-Lorem’s mission to provide personalized experimental treatments free for life to nano-rare patients. 

00:00 – Introduction & Sponsor Message  Stan introduces the episode and explains the importance of the RNA World to nano-rare medicine. 

02:15 – Why RNA Science Changed Everything  How RNA discoveries became foundational to modern genetic therapies. 

05:10 – The Scientific Wars Over Small Nuclear RNAs  The fierce debates among scientists about whether snRNAs were real or experimental artifacts. 

09:40 – What Science Is Really Like Behind the Scenes  Stan discusses the emotional and competitive nature of scientific discovery. 

13:00 – Antisense Technology & the Road to Spinraza  How decades of RNA research led to breakthrough treatments for spinal muscular atrophy. 

17:30 – Lessons From Evolution  Why evolution reuses successful molecular strategies to create complex life. 

22:15 – Families of Genes, Proteins & Molecular Efficiency  How biological systems adapt and customize molecular functions. 

26:00 – Life as an Information System  Stan explains DNA, RNA, proteins, and cells through the lens of information theory. 

29:00 – Final Thoughts: Humanity Wins Through Science  Why scientific perseverance ultimately benefits patients and society. 

In Realizing Hope for Layken, Stan Crooke speaks with Callan Pleasant about her daughter Layken and their journey with HNRNPH2. 

Callan shares the early signs, the long road to diagnosis, and what it takes to navigate care while holding onto hope. Through n-Lorem, Layken’s story is moving forward with new possibility. 

Listen to the full conversation with Callan Pleasant. 

Show Notes: 

• 1:20 – Introduction of special guest Callan Pleasant and her family, namely her daughter Layken 
• 3:50– Parenthood and speed bumps 
• 7:30 – First medical consultation regarding Layken 
• 9:30 – No such thing as a lazy baby. A second look at Layken 
• 10:40 – Finding a diagnosis: HNRNPH2 
• 13:50 – Feeling alone after realizing Layken has a nano-rare disease 
• 16:30 – Managing frustrations and blaming themselves 
• 20:30 – Managing expectations 
• 23:00 – Challenging Layken to communicate and move 
• 26:30 – Finding solidarity with other families 
• 29:30 – London, Layken's sister 
• 38:40 – An explanation of HNRNPH2 along with signs and symptoms 
• 47:30 – Considering possible treatments and risks 
• 49:30 – Taking a leap of faith and submitting for ASO treatment 
• 54:00 – n-Lorem providing hope through science 
• 56:00 – Layken's first treatment 
• 57:30 – Layken's progress 
• 58:50 – Positive verbal progression 
• 1:01:50 – Callan's advice to families 

In this episode of Realities of the Nano-rare, n-Lorem CEO Stan Crooke sits down with Oliver Glass, Ph.D., MHSc, for an honest and heartfelt conversation about raising a child with DYRK1A syndrome. Together, they discuss the early signs something was wrong, the long search for answers, the realities of daily life, and how their family has adapted to build a new normal. 

From daily challenges to unexpected lessons in resilience, love, and perspective, this episode offers a powerful look inside one family’s journey with rare disease. 

🎧 Listen now and subscribe for more conversations from the nano-rare community. 

Learn more about n-Lorem: https://www.nlorem.org 

Episode Chapters 

0:00 Intro 

1:30 Stan introduces Oliver Glass and his family’s story 

7:30 Early signs and symptoms 

14:20 Running tests and searching for answers 

16:25 The diagnosis journey 

23:00 What is DYRK1A? 

27:45 Life with Ethan today 

32:40 How life looks different as a family 

34:00 When the Glass family first heard about n-Lorem 

36:20 Biggest worries for the future 

38:45 Supporting siblings and balancing attention 

43:00 Advice, reflection, and hindsight 

#RareDisease #DYRK1A #GeneticDisorders #PatientStory #Podcast #nLorem #CaregiverJourney #FamilyStory 

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!

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: Induced Pluripotent Stem Cells or iPSCs

iPSCs are a truly transformative scientific breakthrough that are changing what’s possible for nano-rare patients! They allow us to study, test, and personalize treatments in ways that were unimaginable not long ago. For example, they enable n-Lorem to take easily obtained cells, such as skin cells, grow them and then reprogram them into entirely different cell types of interest, like neurons, cells that exist within the brain and would otherwise be inaccessible without invasive procedures. Incredible!

On This Episode We Discuss:

0:53 – What are induced pluripotent stem cells (iPSCs) why they are essential to n-Lorem and personalized medicine 

4:25 – The origins of iPSCs began with curiosity and the discovery and study of cells 

10:19 – Cell differentiation: How a single cell (fertilized egg) can create such a diverse universe of other types of cells 

18:45 – Terminal differentiation: The final stage of a cell's development reaching its final form 

21:45 – The iPSC breakthrough and the doors they’ve opened for treatments 

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

Read the 2026 Chairman Letter

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.

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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/ 

Email podcast@nlorem.org.

On This Episode We Discuss:

5:40 - What is the frequency range of intrathecal and/or LP administrations? Do the treatments not typically cross the blood brain barrier?

7:06 - How do you administer the ASO to animals - is it according to how you plan to administer to the patient?

7:36 - How do you evaluate the potential on-target toxicity if the nonclinical species does not contain the targeted sequence?

9:35 - How often is safety monitored? Is it only monitored quarterly at the Data/Drug Safety Monitoring Board (DSMB) meetings?

11:03 - How long after an ASO is developed for one child, is it offered to other children? Of course, we know that they will have to submit an application. Does the ASO become potentially available for other children after the first child's 2-year trial is over? Or is it potentially available after just a few doses to confirm safety and efficacy?

14:18 - Are there plans to commercialize drugs for the nano-rare?

16:27 - What proportion of institutions elect to use external / centralized institutional review boards (IRBs)?

18:21 - Will there be a cap of accepted applicants from n-Lorem? The demand will only grow and there’s a fear for some families that there’s a chance of n-Lorem capping the number?

19:44 – Once we have our neurologist team working on getting our child accepted, what else do we need to do? What I guess is our next step? Is there anything we should do in the meantime?

20:31 – What should a parent expect once their application has been accepted to n-Lorem?

21:19 – There are widely varying timelines regarding this process. What as a parent should I expect regarding timing?

22:30 – There are companies and academic scientists that claim to provide ASOs for a fee. What do you think about these providers?

23:40 – Insights: What is n-Lorem learning that will be broadly applicable to the scientific community; Dreaming bigger and hoping for more

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 

Holiday Ornament: https://www.nlorem.org/holiday-ornament-fundraiser/

On this episode:

• 1:18 – Natacha introduction
• 3:00 – Biogen’s path to becoming a founding donor of n-Lorem and giving back to the community
• 4:57 – Why Natacha and Biogen invested in n-Lorem and convincing new individuals to buy into the mission
• 7:19 – Biogen has hosted the n-Lorem Nano-rare Patient Colloquium since 2023
• 9:40 – Biogen and n-Lorem share the connection of tackling difficult tasks to make a difference in the world
• 15:05 – A movement for nano-rare the possibilities it may bring
• 17:45 – Taking advantage of nano-rare learnings and implementing them into drug discovery for larger patient populations

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.

On This Episode We Discuss:

2:10 How n-Lorem decides to give a medicine specifically designed for one person to another individual

8:10 n-Lorem built systems to be able to treat more than one patient with a single drug

11:08 n-Lorem creates medicines for nano-rare genetically caused forms of ALS

15:14 New suggestions about the plasticity of the central nervous system and the future of medicine

19:40 Why science isn’t in a good place and will experience lasting repercussions

25:00 The Colloquium will focus on what we’ve learned at n-Lorem and what was once thought to be impossible is possible

27:34 An update on the quantity of INDs filed and patients treated with an n-Lorem ASO

28:80 The benefits of implementing whole genome sequencing (WGS) at birth

30:37 What surprises have emerged throughout the organizational journey of n-Lorem

NRPC25 registration: https://www.nlorem.org/nano-rare-patient-colloquium-2025/ 

Sponsors

ChemGenes: https://www.chemgenes.com/ 

Honegene: https://www.hongene.com/en 

- 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/ 

Rescue 7 is founded by n-Lorem families. They will host the Family Club at the 2025 Nano-rare Patient Colloquium. Families are invited to stop by, hang out, or drop off their children for fun, firefighting-themed activities while caregivers attend the event. Get to meet the first responder volunteers, Luke Rosen, and Raena and Frank Vrtochnick in this episode of the Patient Empowerment Program Podcast!

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/ 

• 2:12 The idea that a missed or delayed developmental step can lead to permanent deficits might not be true
• 3:30 Observations that support the conclusions that developmental deficits aren't permanent unless they cause structural damage, like microcephaly, bone or skull deformities, or organ malformation
• 5:55 ASO treatment can dramatically enhance muscle strength
• 7:54 Abnormal movements and the inability to control movement
• 11:30 The damage seizures cause lead to further developmental delays
• 12:46 We’ve observed improvement in those with ataxia, or dizziness
• 14:25 Improved cognition observed in patients with various mutations, genes, and forms of intellectual disability
• 15:00 Recovery of speech and improvements in autistic features, such as intellectual disability, and other associated manifestations
• 16:10 Severe neuropathic pain makes development difficult, and reduction in pain has been observed
• 16:40 Ongoing issues with autonomic nervous system control—including blood pressure, heart rate, breathing, light response, and digestive and urinary function—are debilitating and make normal development nearly impossible
• 18:00 The implications of these observations are transforming the scientific community’s understanding of the brain and central nervous system

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/ 

- 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/ 

n-Lorem's DSMB is chaired by Dr. Eugene Schneider, Executive Vice President and Chief Clinical Development and Operations Officer at Ionis Pharmaceuticals.

On This Episode We Discuss:

• 2:20 – What is the Data Safety Monitoring Board at n-Lorem?
• 6:50 – Monitoring the data from each and every treated n-Lorem patient is essential
• 9:40 – The DSMB consists of a collection of physicians and other experts
• 13:20 – As the number of n-Lorem patients grows, the DSMB’s responsibilities have expanded significantly—yet members remain deeply committed to supporting the mission
• 17:05 – The DSMB’s goal is to avoid any ASO-related serious adverse events (SAEs) and minimize adverse events
• 19:20 – During his time as Chair of the DSMB, Eugene has learned lessons in patience and humility
• 21:00 The judgements of monitoring boards can and will affect lives

Links: n-Lorem 2025 Nano-rare Patient Colloquium: https://www.nlorem.org/nano-rare-patient-colloquium-2025/ 

Donate to support n-Lorem programs: https://www.nlorem.org/donate/ 

Hongene Biotech: https://www.hongene.com/ 

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/ 

On This Episode We Discuss: 1:23 - What are Induced Pluripotent Stem Cells? 5:45 - Chromatin – compressed DNA and proteins 9:13 - Differentiation and de-differentiation 10:26 - Transcription and transcription factors 12:35 - Why are iPSCs important? 15:20 - Making iPSC and re-differentiating them into the cells we study is time consuming and expensive Important Links: n-Lorem 2025 Nano-rare Patient Colloquium - https://www.nlorem.org/nano-rare-patient-colloquium-2025/ 

Support nano-rare with a donation to n-Lorem: https://www.nlorem.org/donate/  Learn about Hongene Biotech: https://hongene.com/ 

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

- 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 

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/ 

“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 

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

📞 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/

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/ 

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.

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 

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/

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 podcast@nlorem.org.

Question Bank:

1. 2:15 How do you think the event went this year?
2. 6:05 Were observations of benefit expected in patients so quickly? 
3. 9:47 What do you expect the number of patients treated to be next year?
4. 10:57 Do you have a message to supporters?
5. 12:30 Were there any disappointments from the colloquium?
6. 13:21 What are the most important things that n-Lorem has learned this year? 
7. 16:13 Do you think n-Lorem’s processes will be outlined every year at the event?
8. 18:05 How is AI incorporated at n-Lorem?
9. 19:10 Does your recently announced deal with GondolaBio reflect the sustainability strategy discussed at the event?
10. 20:53 n-Lorem is celebrating 5 years in 2025. Did you expect the foundation to be where it is today?
11. 21:28 Does n-Lorem plan to expand into Europe and elsewhere?

Make hope possible with a donation.

To submit questions for our upcoming Q&A episode, email podcast@nlorem.org. We can’t wait to hear from you! 2024 Colloquium Recap

On this episode:

• 2:07 Daphne Graskewicz-Prado, ASO The Perilous Journey to Diagnosis and Treatment for Nano-rare
• 9:35 Ryan Strankowski and Dr, Nelson Leung, Ryan’s Journey and Clinical Experience
• 15:55 Luke Rosen, Megan Hedstrom, and Dr. Jennifer Bain, Susannah’s & Sloane’s Journeys and Unique Clinical Experiences
• 21:49 Kelley Dalby and Dr. Olivia Kim-McManus, Connor’s Journey and Clinical Experience
• 30:00 Dr. Julie Ziobro and Dr. Horacio Kaufmann, Building a Nano-rare Network and Managing Institutional Challenges
• 37:38 Dr. Andrew Lo and Dr. Alan Lotvin, Innovative Ways to Support Nano-rare
• 42:30 Dr. Toby Ferguson, Dr. Liz Berry-Kravis, and Dr. Eugene Shneider, Changing the World One Patient at a Time
• 47:30 Dr. Kate Dawson, What It Means to be a Parter with n-Lorem for Nano-rare
• 50:23 Dr. Stanley Crooke, Providing Hope for a Better Future, One Nano-rare Patient at a Time

Susannah's Story (May 25, 2022)

Donate

2024 Nano-rare Patient Colloquium

On This Episode We Discuss:

• 3:10 Susannah's KIF1A mutation
• 5:50 Luke and his wife Sally changed their careers to help find a treatment for KIF1A
• 7:23 How Susannah's family first heard of n-Lorem
• 8:43 Jen on the Columbia University Medical Center team and the decision to treat Susannah
• 12:25 Luke's experience bringing his daughter to receive an experimental ASO treatment for the first time
• 14:30 The positive outcomes and observations of Susannah's treatment
• 26:15 What Dr. Bain has learned since treating Susannah
• 29:15 Luke on the impact and importance of the little things
• 31:15 Advice to other parents
• 35:40 Being part of a community of nano-rare patients and families

2:21 How many Investigational New Drugs (INDs) has n-Lorem filed? 

5:22 How many patients treated with an n-Lorem ASO have been on therapy long enough to observe a benefit? 

6:50 What does it mean for a patient like Susannah who has experienced a significant decrease in behavioral arrest incidents since receiving treatment 

9:39 Providing ASOs to patients earlier 

13:25 INDs for the ‘n-of-few' 

23:15 Introducing Whole Genome Sequencing (WGS) for all newborns 

29:05 Stan’s perspective on leadership 

33:50 n-Lorem's goals for the 2024 Nano-rare Patient Colloquium

Register for the 2024 Nano-rare Patient Colloquium  Donate

Biogen.com

On this episode we discuss:

2:40 Hongene Biotech and what do they do

8:09 The early days of nucleoside building blocks and maturation of Hongene

12:00 Hongene is a strong supporter of n-Lorem. Why?

15:30 David’s origins in the chemistry field

17:38 Incremental progress that has been made in science and manufacturing

Links:

2024 Colloquium - https://www.nlorem.org/nano-rare-patient-colloquium-2024/

Make Hope Possible with a Donation - https://www.nlorem.org/donate/

Hongene - https://www.hongene.com/

On This Episode We Discuss:

• Questions we can answer and teach us about health and disease and opportunities to treat more common diseases
• What are all the functions of human genes?
• Are there gene products that have redundant functions?
• Do identical mutations cause identical phenotypes?
• n-Lorem can demonstrate that ASOs work on general types of disease challenges

On This Episode We Discuss:

• Two most common words in medicine: Health and Disease
• The Scientific Method
• The Importance of Single Variables
• Orthogonal Thinking
• We Are at a Unique Moment in Medical History
• Genomics
• Advances in Omics
• Biological Networks and AI
• Facile Collection, Maintenance, Growth and Differentiation in the Lab
• Antisense Technology

In This Episode We Discuss:

3:05 – Paul's origins in business and finance

4:32 - Investment banking is different than traditional banking

7:27 – Opposites attract – Meeting his wife, Andrea, and starting a family through adoption

10:06 – Paul’s son, Tayson, has a progressive brain disorder known as DRPLA, which is caused by a mutation in the ATN1 gene; Discovering the idea of n-Lorem

16:03 – Tayson’s journey to a diagnosis

23:00 – The deterioration of his abilities over the years

25:00 – The progress Paul has observed in his son since initial treatment

Links:

Take our survey and receive an n-Lorem Store coupon code

Register for the 2024 Nano-rare Patient Colloquium / October 30-31, 2024

Make Hope Possible with a donation

Recently a report on one of our patients with an ion channel mutation was published in Endpoints News highlighting the power of our technology for these disorders. Check it out by clicking the link below.

Endpoints News (endpts.com) A teenager faced constant seizures. Could a drug developed just for him stop them?

Podcast Awards - The People's Choice

Survey – Patient Empowerment Program Podcast

Register for the 2024 Nano-rare Patient Colloquium

On This Episode We Discuss:

• Defining Ion Channels and Ions
• Health, Homeostasis, and Biological Buffering
• Multiple forms of the same gene
• Multiple Isoforms of Gene Product from the same gene
• Network redundancy
• Ion Channels are different

The Human Body and Barriers

The Four Tubes – Enteral, Respiratory, Urinary, and the Central Nervous System (CNS) tube

How The Body Constructs Barriers

What is Cerebrospinal Fluid (CSF)

The Blood-Brain Barrier (BBB)

The Types of Molecules That Are Admitted to and Excluded From the CNS

Intrathecal Administration of Drugs

Outwitting the Blood-Brain Barrier

Survey Link – Patient Empowerment Program Podcast: https://forms.office.com/r/1ik9WNs7QB

Register for the 2024 Nano-rare Patient Colloquium: https://www.nlorem.org/nano-rare-patient-colloquium-2024/

On This Episode We Discuss:

• Inspired to study biology at the University of Crete
• Leaving Greece to attend grad school at the University of Oxford
• An internship led Nadina to the world of RNA
• Leaving academia to impact lives
• Lessons learned from experiencing drug discovery and development
• The reason she joined n-Lorem
• Day-to-day activities as Director of ASO Design and discovery
• n-Lorem’s internal research management committee to make key decisions regarding programs
• Ongoing research at n-Lorem to enhance allele selectivity
• Stan Crooke on why he pioneered antisense technology

Register for the 2024 NRPC: https://www.nlorem.org/2024-nano-rare-patient-colloquium-registration-form/

On This Episode We Discuss:

• Anna’s life before her symptoms appeared
• The road to a diagnosis and treatment– from Germany to New York City
• Neil Shneider and his work with ASOs
• The struggles of a family fighting a nano-rare disorder
• Anna’s mutation
• Anna’s remarkable progress

Order your Mother's Day card by May 6, 2024! All proceed support nano-rare patients.

On This Episode We Discuss:

• How Zoe met her Husband, Mostyn’s father
• Zoe’s Violin origins and playing with Rod Stewart
• Mostyn’s journey to a diagnosis
• Zoe’s advice for parents observing abnormalities in their child's development
• Mostyn’s severe epilepsy
• A road trip to Boston Children’s Hospital in the middle of winter
• The ‘unlucky’ diagnosis of KCNB1
• For-profit companies promising false hope

On This Episode We Discuss:

1:55 When Dr. McManus became interested in pediatric neurology and epilepsy

4:00 What ion channels do and why they play a role in epilepsy

5:17 How often is epilepsy genetically caused?

6:52 Why Dr. McManus and Rady Children’s Hospital choose to invest time and resources in helping nano-rare patients.

11:50 Bringing people together for a single forum at the Nano-rare Patient Colloquium inspires collaboration between groups

14:43 The importance of a network of treating physicians and institutions and sharing experiences and lessons learned

17:58 Interest within Rady Children’s Hospital regarding nano-rare patient treatment and ASOs

21:45 A Physician’s Perspective of Nano-rare and n-Lorem

On This Episode We Discuss:

• The nature of a SNP
• Pre-mature-m-RNA effects
• Indels can disrupt the reading frame
• Defining Alleles, Homozygous, Heterozygous, and Compound Heterozygous
• The difference between whole exome and genome sequencing
• How we, at n-Lorem, decide which patients are amendable to ASO treatments
• How we design ASOs to take advantage of different post-RNA binding mechanisms
• Mechanisms: Non-allele selective RNAse H1, Allele-selective RNAse H1, and Splicing ASOs

On This Episode We Discuss:

• Your genetic alphabet – nucleotides
• How to think about DNA Replication
• Types of mutations
• What is an SNP and why you should care
• Indels
• The genetic code
• How genetic information is translated into a protein

On this episode, we discuss:

0:56 The importance of hope

3:38 Meeting other nano-rare caregivers and staying connected

6:48 The Nano-rare Patient Colloquium is intimate

12:41 Patients in attendance are one of the joys of the NRPC

16:35 Patient Journey - Connor

20:55 Patient Journey - Mostyn

25:27 Patient Journey - Lena

32:32 Patient Journey - Ireland

39:29 Comments from patient father, Luke Rosen

Video: Susannah's Story: Treated with an ASO

1:20 Sarah’s background, early life, and scientific interests

7:20 Thinking about the patient experience while at a Contract Research Organization

8:43 Rare disease trails are relatively new

10:54 Sarah’s son, Ethan, is a nano-rare patient

16:15 How long it took for Ethan to receive a diagnosis

21:35 Ethan's diagnosis and symptoms

25:55 How Sarah heard about n-Lorem

29:30 How does one come to terms with caring for a nano-rare child; How do parents continue looking for opportunities of hope when they may feel hopeless

32:58 What Sarah has learned while at n-Lorem

36:48 The biggest surprises Sarah has encountered during her journey at n-Lorem

Do you have a question you want to ask Stan Crooke? Email podcast@nlorem.org for a chance to be featured in a future episode.

For general questions, email info@nlorem.org.

In this episode we answer:

08:25 As you are successful in discovering and developing individualized ASO for nano-rare patients, do you envision creating a library of ASOs that would be available to patients across the world?

10:29 For disease organization/patient advocacy groups that have several patients with the same mutation, should they apply for treatment as a group or separately?

13:16 Would an ASO developed for one patient work for another patient with a mutation in the same gene?

14:29 What's a SNP?

16:19 As a nano-rare family member, I have never been so inspired in an opening address as what was provided at the 2023 colloquium by Stan Crooke. Given the mission of n-Lorem, I don’t understand how any researching neurologist (or any researcher in the space) would not want to be at the absolute forefront of what n-Lorem is doing. Why do you think there is such an obstacle to being a part of an organization that has for the first time an opportunity to move the needle in such a meaningful way?

20:16 How would you describe the relationship between n-Lorem and the research physician, and what should patients expect from each side?

23:44 What do you mean by an optimized ASO?

24:59 Would you expect to see better results from ASO treatment in patients who are younger versus older?

28:10 The FDA has certain designations for program review (Fast Track, Orphan, etc,), is there anything like that for nano-rare patients?

29:35 I realize that there was significant work done in 2023 to streamline n-Lorem’s operations. Which processes in the workflow do you believe can still be optimized to help streamline patient programs?

31:35 Has there been a change in the amount of time it takes to process a patient and develop and ASO since the Foundation started?

32:50 Do you reach out to patients which presumably have ‘ASO-able’ genetic mutations?

34:12 Do you have any activities or ongoing projects that would help educate and train physicians who might be interested in participating with n-Lorem?

36:05 Are there any new updates regarding the 2024 Nano-rare Patient Colloquium?

41:36 Say a patient is denied from n-Lorem because at the time of their application submission, the Access to Treatment Committee declares that the program is not amendable to the current technology and/or ASO strategies, but new data/technology comes out that suggests that patient’s program has revived potential... will the ATTC automatically reassess the case or does a physician have to re-apply the patient to n-Lorem?

n-Lorem is different than standard drug development settings. Every risk/benefit decision that n-Lorem makes is in the context of the individual patient’s symptoms, status, and needs. While we cannot promise benefit, we can promise that we will do our very best in the creation of an optimal medicine.

On This Episode We Discuss:

• Risk/benefit decisions
• n-Lorem is different
• We cannot make promises
• Communicating about risk
• Perceptions concerning control
• Exposure and risk
• Compression
• Omission
• Timing
• Official positions affect our perceptions
• Anchoring and communicating risk

On This Episode We Discuss:

• Why nano-rare patients and their families need to think effectively about risk
• Risk vignettes: infectious diseases, automobile and smoking deaths
• A rational way to think about risk
• Being comfortable with a probabilistic reality
• The 80/20 rule
• Considering consequences
• The process to assess risk
• Getting serious about risk/benefit evaluations
• Risk/benefit judgements

On This Episode We Discuss:

• 2:45 Joining the Amy on a whim
• 4:30 Serving in Kosovo and Germany
• 6:00 Learning that his mother was diagnosed with Huntington’s disease (HD)
• 10:25 Seeking information and diving into the world of Biology and HD
• 14:52 Deciding to have children when there was a chance that they’d inherit the disease and utilizing preimplantation genetic diagnosis (PGD)
• 18:30 Watching Ionis make initial progress on an ASO for Huntington’s disease
• 23:10 How Jeff became involved with n-Lorem
• 27:30 Most important things Jeff has learned during his role at n-Lorem
• 30:38 Helping people is motivating
• 32:11 Nano-rare patients teach us a lot about science
• 33:57 Jeff expects to receive an ASO treatment one day
• 35:22 n-Lorem is on your side

On This Episode We Discuss:

• 0:46 Working on the Alaska Oil Pipeline as a 17-year-old
• 4:30 Saving money young and becoming an entrepreneur
• 7:05 Following trends and founding Lululemon
• 8:36 Chip’s initial dream and vision for Lululemon
• 11:45 Combining Italian design ethics with quality western fabrics for an amazing Lulu product
• 14:20 The feeling of leaving the Lululemon Board of Directors
• 17:00 The takeaways from Joseph Heller’s Catch 22 and Something Happened
• 24:15 Reading the top 100 biographies and admiring those with integrity
• 33:44 Using the culture of an organization and leadership as a strategic advantage
• 38:18 Facioscapulohumeral muscular dystrophy (FSHD)
• 40:05 Chip on losing muscle when exercise and movement is so necessary for his way of life
• 44:27 Climbing Mount Kilimanjaro with FSHD
• 46:58 Chip’s advice to those suffering from rare diseases and their caregivers
• 49:24 What progress that has been made to find a treatment for FSHD
• 52:35 Why Chip and SOLVE FSHD donated to help fund the funded the laboratory at n-Lorem

On This Episode We Discuss:

• “I Sing The Body Electric”
• Hemo and chemo-electric machines
• The nervous systems
• Autonomic nervous system manages many organs and involuntary functions
• Sympathetic and parasympathetic nerves

• 2:02 How rare disease is defined at Takeda
• 4:10 Rare disease units at Takeda
• 5:23 How Takeda economically justifies half of their pipeline being rare disease drugs
• 9:06 The price of rare disease drugs is too high
• 12:15 Why rare disease efforts are often associated with hematology
• 14:57 What Dr. Curran enjoys about leading Takeda's rare genetics and hematology therapeutic unit
• 16:42 Dr. Curran's professional journey
• 20:50 Takeda's choice to support n-Lorem

On this episode we discuss:

• Controlling inflammatory processes
• Liver failure
• Genetic disease pathways
• Drug metabolism
• Fatty liver
• Blood tests signal liver disfunction

On This Episode We Discuss:

• Producing countless small chemical metabolites
• Controlling iron homeostasis
• The liver and the gut microbiome
• Combatting starvation and triggering appetite
• Managing glucose levels

On This Episode We Discuss:

• 0:00 What is Ciitizen?
• 3:14 The difficulty of sharing medical records before Ciitizen
• 5:55 Gay’s daughter, Lilly, is an n-Lorem patient
• 10:00 Finding an initial pediatrician to help Gay and her family diagnose and understand Lilly’s gene mutation
• 11:45 Lilly’s nightly seizures and wondering what it would take to receive a diagnosis
• 15:05 How caffeine helps Lilly and others with ADCY5 mutations
• 18:35 What Lilly is doing nowadays
• 19:48 How Lilly’s genes were sequenced
• 21:00 Advocating to introduce newborn sequencing into newborn screenings
• 23:30 What was known upon diagnosis and other’s with ADCY5 mutations
• 28:13 Lessons that Gay learned from her 25+ years of rare disease care and advocacy
• 33:19 The progress n-Lorem has made since inception

On this episode we discuss:

• Obstruction of the airways due to smoking, cancer, infectious diseases, etc
• Obstruction of pulmonary blood flow
• Obstruction of gas exchange
• Interference with the inflation and deflation of lungs

We launched our Patient Empowerment Program with the purpose of building a nano-rare community and establishing a forum in which the voices of patients, advocates, and experts can come together focused on the nano-rare patient. We’re happy to report that we believe we have done just that – create a forum for our nano-rare community.

To celebrate one year of the Patient Empowerment Program, we compiled clips from previous interviews to form a special podcast episode centered around “community” and it really does take a “rare” community to do what we do.

On This Episode We Discuss:

- Being a dream merchant and driving a dream into a real therapeutic platform

- Founding of Regulus and the synergy between Ionis and Alnylam throughout the years

- What happens when two very competitive CEO-scientists have competing drugs

- Overcoming their differences

- Giving hope to a patient and their family with nano-rare diseases is powerful

- Saving the world one life at a time

- Bringing ASO and RNAi technologies together to collaboratively help nano-rare patients

- A sustainable non-profit model?

- Hope – a powerful thing to lose and an important thing to recover

Question Bank:

- How do you apply to be an n-Lorem patient and who do you need on your team to help? 05:26

- How does the Foundation assess cases? 05:26

- Once a patient is accepted, what is the best way to track the progress of the ASO program? 12:45

- Any advice for when seeking information from a research physician who isn’t communicative? 14:05

- How often should a patient expect to hear communication from a research physician? 15:50

- What is hydrocephalus, and should patients be concerned about the side effect? 19:30

- If side effects occur in treated patients, will subsequent patients be notified in real time? 30:55

- What is the difference between an ASO and gene therapy? 33:55

- How is n-Lorem defining an “optimal ASO”? 37:20

- Can n-Lorem help patients who are severely advanced in their disease? 44:10

- How can treating one person can lead to breakthroughs for many more? 39:40

- What is Stan’s favorite success story from his career? 46:20

On This Episode We Discuss:

• Andy’s upbringing among physicians and pharmaceutical entrepreneurs
• Traveling the world to launch Humera
• Baring the frigid Boston winters at MIT
• Inspiration to found Unipr
• How biotech and pharmaceutical organizations can use Unipr to increase efficiency
• The partnership between Unipr and n-Lorem
• Unipr’s focus areas: Increasing the probability of success, decreasing the operational costs, and decreasing the cycle time for drug development
• Why Andy would donate himself to help n-Lorem

On This Episode We Discuss:

• Target ALS’ innovative model
• Accelerating ALS research through collaboration
• How a single nano-rare study can inform the ALS research landscape
• The importance of understanding the fundamental biology behind ALS
• Committing to fight all forms of ALS
• Target AlS’ support for n-Lorem and Columbia University’s Silence ALS Initiative

Visit www.nlorem.org

On This Episode We Discuss:

• Dan’s inspiration to bring the Olympic Games to NYC
• 3 things he learned as a CEO
• Dealing with the reality of being diagnosed with ALS
• Shifting his perception of life
• How ALS has impacted his bloodline
• Scaling up Target ALS and fighting for the lives of every ALS patient

n-Lorem is accepting nano-rare kidney patients for treatment. Information about the application process and can be found at www.nlorem.org/access

Jamie Macdonald, CEO of Parexel, joins Stan to discuss the moment he realized his desire to make a difference, Parexel’s role in clinical trials and their partnership with n-Lorem aimed to serve patients.

Stan talks with a rare disease treatment advocate and the CEO, President and Founder of Ultragenyx, Emil Kakkis, MD, PhD, about why he has dedicated his career to supporting the rare disease community, what led him to establish the EveryLife Foundation, and the origins of Ultragenyx. Because of the debilitating and often quick progression of rare disease patients, Emil believes that regulatory agencies should modify the way they approach clinical trials for these individuals. Far too often, policies leave patients stuck waiting and hoping for treatment while their symptoms worsen, causing permanent damage.

Do you have a question that you’d like to ask Stan Crooke? Stan will be taking questions directly from you and other podcast listeners and dedicating an entire episode towards answering your questions! To submit a question for the upcoming Q&A episode, email podcast@nlorem.org with the subject line labeled “podcast question”. If you wish to be identified, mention your name in the email. If not, we will keep your submission anonymous. We can't wait to hear from you!

Do you have a question that you’d like to ask Stan Crooke? Stan will be taking questions directly from you and other podcast listeners and dedicating an entire episode towards answering your questions! To submit a question for the upcoming Q&A episode, email podcast@nlorem.org with the subject line labeled “podcast question”. If you wish to be identified, mention your name in the email. If not, we will keep your submission anonymous. We cannot wait to hear from you!

When considering if the technology he led the creation of could be a viable way to develop a drug for a single patient, addressing their specific mutation, Dr. Crooke felt that he had to try, patients were dying without access to any treatment because they were just too rare. So began n-Lorem. As expected, developing an optimal ASO for a single patient is not an easy or simple process. Quality must lead every step and only optimal ASOs can reach patients.

Learn our science and processes behind the discovery and development of personalized ASO medicines for each of our nano-rare patients. n-Lorem’s mission is to provide hope and potential help to nano-rare patients – for free, for life; a mission that was impossible just a few years ago. This enables the non-profit approach that we believe is the only way to address the needs of nano-rare patients. Thanks to our partners like Argonaut, we are able to provide hope and potential help to patients today and tomorrow.

Compared to other 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 are designed to bind precisely with RNA, modifying the process of creating a disease-causing protein. Thereby making ASOs highly specific and a powerful drug discovery technology for nano-rare patients, who need a therapeutic approach that targets their specific gene mutation.

Learn more about Wendy Erler on twitter @wendy_erler

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mAbs are man-designed, biologically made proteins and typically, are 60-70 thousand Daltons. Clearly, they are in orders of magnitude larger than SMDs and, as you’d expect, they behave very differently from SMDs. Because mAbs contain more information than SMDs, they are generally more specific. Though mAbs are much larger than SMDs, only a little bit of information in the mAbs is used to specifically interact with their target and yet, all that chemical information in the protein can interact with many other things and thus cause problems.

These are more specific than SMDs and can target a single site on a protein or chemical. RNA-targeted drugs, like antisense oligonucleotides (ASOs) and SiRNAs, use genetic information to target a specific site on an RNA. n-Lorem takes advantage of the specificity and versatility of ASO technology. ASOs are highly specific, and we can continuously learn from successes and failures of the technology to predict how the next one will behave. Discover the in-depth differences between the three platforms, their triumphs and failures in modern drug discovery, their benefits and limitations, and why gene therapy is not on the list of drug discovery platforms… yet.

As pharmacologists and physicians interested in treating patients with drugs, we are interested in several properties that all drugs have. These include the mechanisms by which the desired objective is induced, pharmacodynamics, the mechanisms by which the drugs may induce side effects, toxicology, and the mechanisms by which the body distributes and clears a drug from the body, pharmacokinetics. Put simply, we are interested both in what the drug does to the body and what the body does to the drug.

Because drugs are chemicals and chemical reactions depend on collisions between two or more chemicals, drug effects are concentration dependent. We adjust the concentration of a drug in the body by adjusting the dose. All effects of drugs, with the possible exception of allergic reactions, are dose dependent. Therefore, we are interested in the doses that produce a desired effect and the doses that may produce undesired effects, or adverse events (side effects). A drug that produces a desired effect at a much lower dose than the dose required to produce an adverse event is usually considered a better drug. When we assess the difference between the dose that produces a desired effect and a dose that produces an adverse event, we are now analyzing a drug performance in a sophisticated way, and we are thinking about the term therapeutic index. This is the key parameter that you should always be thinking about when you use a drug.

There are podcasts about genetics and rare diseases, but we didn’t find one focused on nano-rare diseases, conditions that affect 30 or less people in the world.

Listen to this trailer to hear a sneak peak at what’s coming up on the podcast.

There are going to be two types of episodes on this podcast, interviews and lessons. All episodes are hosted by biotech titian, Dr. Stan Crooke. He is the Founder, Chairman and CEO of the n-Lorem Foundation.

Here’s how you can support our podcast launch: Rate & Review the podcast on Apple, Spotify, or wherever you listen. This truly helps us climb the charts and allow others to find the show. After you do that send it to a friend who you think will enjoy our podcast.

And good news, you don’t have to wait long for the podcast, we are launching next week on May 25th, 2022 with three new episodes! So hit that subscribe button.

For more information about n-Lorem and our podcast visit nlorem.org. Any questions can be sent into podcast@nlorem.org. Stay updated with the show by following us on social media, search “n-Lorem” on all platforms.

Our videographer is Jon Magnuson of Mightyone Productions. Our producers are Kim Butler, Amy Williford, Jon Magnuson, and myself, Kira Dineen of "DNA Today".