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/