As the 2025 Nano-rare Patient Colloquium approaches, we welcome back Transmitter Features Editor Brady Huggett to guest-host this episode of the Patient Empowerment Program podcast. Brady sits down with n-Lorem founder and CEO, Dr. Stan Crooke, to reflect onto reflect on the strides made over the past year—insights that will help shape the discussions at this year’s Colloquium.

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

The ‘Hero of n-Lorem’ Award is a recognition given to an individual volunteer or organization that has made substantial contributions to n-Lorem and our nano-rare patients. This honor recognizes our ‘unsung heroes’, those who have gone the extra mile, taken time away from their schedules and families and leveraged their expertise and contacts to support n-Lorem’s mission to provide hope and potential help to nano-rare patients. On this episode of the Patient Empowerment Program podcast, we welcome three of our five 2025 Heroes for a conversation about their inspiration to take action:

- Wendy Erler, Senior Vice President, Patient Affairs, Sarepta Therapeutics

- Richard S. Geary, Ph.D., Chief Development Officer, Executive Vice President of Development, Ionis Pharmaceuticals

- Scott Henry, Ph.D., DABT, SVP, Nonclinical Development, Ionis Pharmaceuticals

Sponsors:

ChemGenes

Hongene Biotech

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

Rescue 7 is dedicated to serving the most vulnerable patient communities with care, compassion, and critical support. Inspired by the traditions of Fire Departments, Police Departments, and Military service worldwide, their programs go beyond emergency response. From patient transportation to sibling support initiatives, as well as emergency disaster relief efforts — Rescue 7 is there. Always ready and there when you need them.

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!

Sarah and Ryan Marta, proud parents of three girls from Central Texas, began noticing that their middle daughter, Kinsley, was slow to reach mobility milestones in her early years. During a visit to a friend’s house, concerns about her vision were raised, prompting a check-up. What began as a single hospital visit quickly turned into many. An MRI revealed abnormal levels of white matter in Kinsley’s brain—leading to the devastating and confusing diagnosis of a nano-rare neurodegenerative disease called TUBB4A.

Looking high and low for help, they eventually discovered n-Lorem, a non-profit that discovers and develops personalized medicines for extremely rare individuals like Kinsley.

Kinsley is lively and cheerful with infectious laughter and a bright smile that lights up every room. She loves singing at the top of her lungs, swinging in the fresh air, and spending endless hours playing with her sisters and cousins. Kinsley uses a mobility walker to get around, but one of her biggest dreams is to run. When asked what she’d do after running, she simply says, “I’d run some more.”

On This Episode We Discuss:

2:35 - Early signs of Kinsley’s disease and her TUBB4A diagnosis

4:00 - Fight or flight – Sarah and Ryan did all they could to seek help

7:30 - Defining TUBB4A

9:40 - Kinsley's challenges today

11:00 - The impact rare diseases have on families

14:40 – Kinsley wants to do more, and an n-Lorem medicine provides optimism

Links: 2025 Nano-rare Patient Colloquium Agenda and Registration - https://www.nlorem.org/nano-rare-patient-colloquium-2025/

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

Hongene Biotech - https://hongene.com/

Emerging observations from our work at n-Lorem suggest that not all developmental delays are permanent. In the absence of structural damage—such as microcephaly, congenital deformities of the skull or bones, or organ malformations—there appears to be potential for improvement in movement disorders, cognition, autistic features, and more. These insights point to a level of resilience and plasticity in the central nervous system that may be greater than previously believed, and they are beginning to reshape how the scientific community understands the brain. On This Episode We Discuss:

• 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/

At n-Lorem, every investment decision carries real weight by directly affecting the nano-rare patients we serve. We think very deeply about each decision of how to invest the limited and precious dollars that we have. But what about investing in basic research to advance antisense oligonucleotide (ASO) technology for the future? Certainly, most of the money should and is being put towards creating ASOs to help patients in need today. Meanwhile, it is also our belief that we must invest to continue innovating and, in this episode, we explore the research occurring at n-Lorem today that will lead to better treatments for more nano-rare patients tomorrow. On this episode we discuss: - ASO technology is still evolving unlike other validated drug discovery technologies

- Nano-rare patients need more from ASO technology

- Reasons n-Lorem are unable to help more patients

• Loss of function mutations
• Mutations that cause dysfunction of an organ to which ASOs distribute at only high doses
• Innate immune activation
• Challenges in creating allele-selective ASOs

- Solutions to these challenges are possible and we know how to do it

• Advances in loss of function mutations
• Targeted delivery to muscle, the immune system, the gut and heart
• Controlling innate immune activation
• Enhanced allele-selectivity

Links:

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

Donate - https://www.nlorem.org/donate/

The Data Safety Monitoring Board (DSMB) is composed of distinguished, independent experts in antisense oligonucleotide (ASO) technology, clinical trial design and evaluation, and drug development. Many are also dedicated clinicians who care for patients with rare diseases. This board provides unbiased safety oversight by reviewing accumulated data from all investigator-initiated studies involving n-Lorem’s ASO medicines.

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/

Connor Gooley is the first patient ever treated with an ASO for TUBB4A-Related Leukodystrophy, a condition that severely disrupts his nervous system, slows nerve impulses, and impairs his fine motor skills. As a result, Connor cannot speak, walk, sit up on his own, or chew well. Still, he manages to army crawl, propel himself in his wheelchair, and use a gait trainer. He’s also remarkably resilient—rarely crying or complaining despite the daily challenges he faces.

In this episode of the Patient Empowerment Program, Connor’s parents, Diana and Mike, share their family’s journey from diagnosis to treatment and reflect on their observations of Connor after more than six months on an n-Lorem discovered and developed treatment.

On This Episode We Discuss:

1:33 Shaking eyes were the first sign of Connor’s rare disease

4:10 An MRI revealed little to no myelin, leading to whole genome sequencing and an eventual TUBB4A genetic mutation diagnosis

7:10 Connecting with another family with the same mutation

10:00 Finding n-Lorem through a ‘seeking patient candidates’ advertisement in a Global Genes annual report

12:26 Contextualizing Connor’s TUBB4A mutation in simple terms

21:19 How rare diseases affect families and creating a new normal

27:41 Receiving treatment in Boston and contemplating the decision to agree to an experimental treatment for their son

32:00 Observations after 6 months on treatment

35:45 n-Lorem has given the Gooley family hope for a better future for Connor

Links:

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

Donate to n-Lorem / Support nano-rare: https://www.nlorem.org/donate/

n-Lorem 2025 NRPC: https://www.nlorem.org/nano-rare-patient-colloquium-2025/