By Luke Rosen, Published on Medium Dec 21, 2022
Our daughter is a superhero. She is a pioneer, and she is changing. Susannah has a rare neurodegenerative condition called KIF1A Associated Neurological Disorder, or KAND. She joins a handful of people in a united community each with very real desperation and hope. Our collective hope is to stop the clock on this disease; to slow progression and curb the severity caused by a constellation of medical enigmas and pain.
Susannah wakes up crying in pain because her dying nerves cause a neuropathy which makes her scream out (in her own way) “My feet are burning on the inside, help me!” We can’t help her. We can’t come to her rescue and make her pain go away. There is no treatment, there is no cure. No remedy for her optic nerve and brain atrophy. We are engulfed in the flames of a ticking clock and the limited time we have to save her. We yearn to stop the clock on her body’s degeneration. No medicine halts nighttime seizures that plague her sleep, or the many broken bones caused by terrifying spasticity and falls. Susannah needs twenty-four hour care and support.
We have hope. Hope is our lifeline. It’s the one commonality every family has. This heterogeneous nightmare affects every patient and every family differently, but hope… hope is something we all share. Hope is alive. Hope is thriving, and hope is the fire blazing throughout every rare community with a seemingly hopeless fate. Hope is critical as families unite to focus on science and medicine. Rare disease families like ours have PhDs in hope.
KIF1A is loaded with medical complexities that rip elements of life from our daughter and others affected by this cruel and unfair disease — a disease which robs life from children. KAND steals life at different speeds for every person with a mutation in the KIF1A gene. No two people are the same, and no two people are affected in an identical way. Sometimes KAND works slowly, methodically blinding and stealing steps over a long period of time. Sometimes KAND outruns the ability for a child to breathe and kills people we love before one can even grasp the joy of parenthood. The difficult reality is that every person, regardless of known outcome, may not be amenable to current genetic-based therapies. We must always have hope.
Our collective goal is to change the trajectory of disease and show the world that a handful of pioneers are proving a concept we never thought would be real. A small group of family-pioneers just might set the stage for a scalable therapeutic before time runs out. We hope.
We relentlessly hope like so many parents that something might happen; that an innovation might suddenly appear to calm the storm of neurodegeneration. We’re close. Nano-rare family groups working collaboratively with scientists represents hope for a future with faster, safer, and effective treatments.
Together our whole rare community is blazing a trail. It’s hard to be the first family in all things. In many ways, it’s been a blind navigation since day one in 2016 when Susannah was diagnosed. But we evolve, we have advocates, patients, families, physicians, sherpas, and scientists who answer our community’s loud calls and love our children. Hope grows with every new and active community member . Our relentless community includes families, researchers, physicians, and ASO developers, each applying expert skillsets and all working selflessly together. Together we work.
In2017 an incredible KIF1A community galvanized, and Susannah was the first in a growing group, each desperate to jumpstart our (now thriving) Natural History Study and drive discovery — and hope. Every member in our nano-rare community faces seemingly impossible challenges. Every community member who travels to conferences, participates in studies, and sacrifices time is a pioneer.
Years later the rare disease community was introduced to an innovative new group: n-Lorem foundation. We shared news of this compassionate program with others in the community to see. Then we consulted Susannah’s physician and decided to apply. After going through the years-long (much shorter today) application process, n-Lorem scientists worked to prove her specific genetic sequence was amenable to antisense experimental treatment. Susannah was dosed in November, 2022. This ASO was entirely funded, researched, developed, and created independently by a ground-breaking endeavor: the n-Lorem Foundation. This N of 1 is built for others to follow. This N of 1 is powered for Susannah’s life to change, and being the first is hard. We hope those who follow Susannah will experience a smooth, safe, effective treatment process because of a handful of brave pioneers. Once again we find ourselves hoping she’s the first of many. We hope desperately that her life changes and the cries of pain disappear from our soundly sleeping, seizure-free child.
KIF1A is a large gene. I can promise you the size of this gene doesn’t compare to the heavy burden every family carries daily. Susannah and her brother are superheroes. Every sibling, every family member, and every community member is impacted. They too are brave pioneers. Susannah’s N of 1 ship is helmed by a remarkable team of researchers, physicians, and passionate ASO developers, each with decades of experience and training. Can this experiment work for people with other mutations in KIF1A? We hope.
The innovators who conceived an organization dedicated to the nano-rare built a brave new model, a model that works. Susannah’s ASO is driven by passionate people with the highest ethical standards. Applications for nano-rare N of 1 experimental trials are de-identified: blinded to a committee of experts who base decisions purely upon genetics, feasibility, chemistry, and potential impact.
We are incredibly fortunate that Susannah is the tip of this nano-rare iceberg; an ASO targeting her precise genetic anomaly, a mutation that is stealing away elements of her life that every child, every human is entitled to. But this experience is not trivial. This N of 1 trial is grueling.
Every bold endeavor starts with a small “N” and this blessing of an experimental treatment is teeming with hope, but it’s so hard. The trial is filled with everyday monitoring, seizure and fall diaries, almost weekly visits to the hospital, and sleepless parents. We know the risks and we fully understood what is at stake when we began our ASO journey. Utter confidence in our expert, passionate guides calmed us. We’re still anxious for every monthly dose; a day that compounds our ever-present guilt for putting her through monthly anesthesia, lumbar puncture, and ascending doses of drug to identify the correct amount needed to fix this toxic gain of function protein in KIF1A. Anxiety, recording every detail, myriad doctor appointments and attention to every daily detail is harder than we ever thought. Quantifying her change is tricky, but it’s real. Her change is countable and clear to family and friends. Tears are different when people speak with Susannah. She sings without prompt, and the blurred veil of disease shows signs of lifting. Change is bliss. But we’re not there yet. We’re close. We’re getting there together.
This consumingly hopeful trial inevitably (and unexpectedly) steals attention from her loving brother and his right to have parents who are truly present for him. This trial takes a toll on relationships. But we have hope.
We know this process will yield very meaningful change for Susannah, no matter how incremental. This process will be easier for those who follow her. Susannah and the few patients suffering from other genetic diseases who came before her carve a pathway of hope. They define that word: pioneer. This is not an overused title for a nearly ten-year-old little girl with painful spasticity, epilepsy, and rapid onset optic nerve atrophy.
Our KIF1A pioneer is laying groundwork for a therapeutic void of constant hospital visits, guilt, and anxiety that accompanies Susannah’s N of 1 trial — a trial we are so thankful to be part of. Like scientists and KIF1A friends, Susannah is a superhero and a pioneer. But this experience is hard. It’s hard to be Susannah. This flight into the relatively unknown is scary. We hope this trial, led by a team of experts with decades of experience who have cured diseases, will change the trajectory of Susannah’s life. We hope our little girl gets better. We see change. We have hope for our community.
We hope this trial will raise awareness and resources to bring treatments to many more. Families with PhDs in hope need to know this is not a cure; however it is hope for a life-changing intervention. Families with PhDs in hope need to know this process is very fluid and time consuming. It takes a long time to create each unique ASO from discovery to development and requires a serious commitment from families to participate. It’s a hard road to be the “1” in this N of 1 trial. But we’re hopeful.
You see, hope is impossible alone. Hope comes from communities of rare families, physicians and scientists forging a united front. The only way to scale this medicine is together. Communities working responsibly together make this epic effort by remarkable physicians, n-Lorem, and the fleet of people working tirelessly behind the scenes a blessing far beyond words on this page. This hope is contagious; a wildfire spreading in a growing, gene agnostic community. When science and families work in harmony as partner-pioneers the floodgates will open. Our girl, together with a handful of others, is the tip of a sword — a sword which hopefully makes these trials possible for people dying from nano-rare genetic diseases. Scientists and physicians dedicate rigorous investigation to understand which mutations are amenable to antisense treatment. No one person is the same, but together we are strong.
The rare community is tough as nails. To be a pioneer is an exhausting, life-changing effort for families, physicians and selfless groups resourcing development of safe ASO’s. It takes communities working in harmony to make N of 1 trials worth every milligram of hope. We have community. We have pioneers. Together our communities are a force of nature. Together we can stop the clock of decline for people suffering from rare genetic diseases like KIF1A. Only together can we march up this mountain of change. Together we have hope.