Case study, published in Nature Medicine, details improvements in nano-rare patient, Susannah’s seizure severity, neurologic function and quality of life

n-Lorem, a nonprofit foundation, announced today the publication of a case study detailing the treatment and initial outcomes for a nano-rare patient who is receiving treatment with a personalized experimental ASO medicine discovered and developed specifically for that patient. In this report, most outcome measures including seizure severity, number of falls, overall speech and quality of life improved after treatment. The study, authored by the patient’s doctors Wendy K. Chung, M.D., Ph.D., of Boston Children’s Hospital, and Jennifer M. Bain, M.D., Ph.D. of Columbia University Irving Medical Center, along with n-Lorem, was published today in Nature Medicine (Zeigler, A., et al. Nature Medicine advanced online publication, Aug 2024).

In this study, the challenges caused by KIF1A-associated neurological disorder (KAND), and the positive impact observed during treatment on Susannah’s neurologic function and quality of life were described. The case study reported that during the 50-day period prior to treatment, Susannah’s parents described 100 and 290 seizures a day. Following her first dose of the personalized experimental ASO medicine developed by n-Lorem, her parents reported the number of seizures dropped to less than 30 a week, where it remained relatively consistent. Similarly, prior to her first dose, Susannah’s ability to walk was severely impaired with an average of 26.2 falls a day. A month after her first dose, her gait improved and the number of falls decreased to a maximum of seven a day, while many days she didn’t fall at all despite being far more active. In addition, researchers noted improvements in her quality of speech, attention level, engagement, ability to interact in group activities and motor function while her cognitive ability remained stable. The patient has now been on ASO treatment for 20 months with a favorable safety and tolerability profile.

“Our goal from the outset with Susannah was to arrest the progression of her disease, which is often fatal. This is the first time a medicine has been able to treat the genetic cause of KAND, halt disease progression and provide meaningful clinical benefit,” said Wendy Chung, M.D., Ph.D., Chair of Pediatrics at Boston Children’s Hospital. “While Susannah’s medicine was designed to work on her specific genetic sequence, we are hopeful that more KAND patients will potentially benefit from this medicine. Our KOALA study is important in this endeavor, as it allows us to evaluate each patient’s clinical status and genetic sequence to identify which patients may potentially be candidates for this medicine.”

“n-Lorem’s approach is truly personalized medicine, where an individual patient’s genetic profile is used to guide treatment of that patient’s disease. In this case, n-Lorem’s ASO was designed to target Susannah’s specific genetic cause of disease in hopes of halting the progression of her neurodegenerative disease,” said Jennifer M. Bain, M.D., Ph.D. Associate Professor of Neurology and Pediatrics at Columbia University Vagelos College of Physicians and Surgeons. “Since starting the treatment, Susannah has made improvements far beyond what we expected. We have been able to track how she has advanced from using a wheelchair much of the day to walking, climbing stairs and even playing basketball with her brother. We are hopeful that what we are learning from Susannah can apply to other KAND patients.”

KAND is a severe neurodevelopmental and neurodegenerative disorder that is often fatal and can cause irreversible brain and optical nerve atrophy, epilepsy, cognitive impairment and peripheral neuropathy. The disorder is caused by more than 100 mutations in KIF1A, and KAND will require multiple ASOs to treat all KAND patients. In an effort to understand how KAND symptoms develop and change over time, Dr. Wendy Chung’s team is conducting the KOALA study (KIF1A Outcome measures, Assessments, Longitudinal And endpoints study) to advance KAND research by performing longitudinal standardized assessments with KAND patients.

“We are beyond thrilled with the improvements that we have observed in Susannah. Prior to treatment, Susannah’s disease had progressed to her being mostly in a wheelchair, approaching nonverbal with debilitating seizures that limited her and her family’s quality of life. Susannah has now been on treatment for more than 20 months and we continue to observe improvements in her mobility, neurological function and quality of life,” said Stanley T. Crooke, M.D., Ph.D., Founder, Chairman and CEO, n-Lorem Foundation.

“Because the KIF1A protein serves a vital function in the body, our approach required the design of an ASO medicine that would target the copy of the gene that had the mutation, while allowing the other copy of the gene that does not contain the mutation to produce normal KIF1A protein. This selective gene targeting of the ASO allows the functional KIF1A protein to be expressed and available for normal cellular function, while removing the toxic KIF1A protein. There is no other technology that is capable of this gene selectivity, only ASO technology,” continued Dr. Crooke. “While we hope to see such dramatic improvements in all of our patients, we understand that may not be the case given the broad diversity of target genes, disease progression and disease severity in our patients.”

n-Lorem discovered and developed a personalized, experimental ASO medicine specific to Susannah’s needs. The first dose was administered in October 2022 by Drs Chung and Bain at Columbia University Irving Medical Center. Susannah remains on treatment at Columbia Medical Center and continues to see increased clinical benefit from this medication.

“Personalized ASO medicines can be incredibly selective and offer significant therapeutic hope for many nano-rare patients. At n-Lorem, we believe that each patient deserves the very best ASO that we can discover, and we have the expertise, knowledge, automation and experience to do just that for our nano-rare patients,” concluded Dr. Crooke. “While we are treating one nano-rare patient at a time, what we are learning from a single patient will help entire patient communities and broaden our understanding of how a single gene mutation can cause devastating diseases. We built n-Lorem knowing that one day we might be treating thousands of nano-rare patients.”

To learn more about Susannah’s story see n-Lorem website, watch this video created after she started receiving treatment or listen to Susannah’s Journey podcast on the n-Lorem Patient Empowerment Program.

About n-Lorem

n-Lorem Foundation is a non-profit organization established to apply the efficiency, versatility and specificity of antisense technology to charitably provide experimental antisense oligonucleotide (ASO) medicines to treat nano-rare patients diagnosed with diseases that are the result of a single genetic defect unique to only one or very few individuals. Nano-rare patients describe a very small group of patients (1-30 worldwide) who, because of their small numbers, have few if any treatment options. n-Lorem Foundation was created to provide hope to these nano-rare patients by developing individualized ASO medicines, which are short strands of modified DNA that can specifically target the transcripts of a defective gene to correct the abnormality. The advantage of experimental ASO medicines is that they can be developed rapidly, inexpensively and are highly specific. To date, n-Lorem received over 280 applications for treatment with more than 130 nano-rare patients approved. n-Lorem was founded by Stanley T. Crooke, M.D., Ph.D., former chairman and CEO of Ionis Pharmaceuticals, who founded Ionis Pharmaceuticals in 1989 and, through his vision and leadership, established the company as the leader in RNA-targeted therapeutics. Follow us on Twitter, Facebook, LinkedIn and YouTube.

To learn more about n-Lorem’s mission at www.nlorem.org, and please consider giving to n-Lorem to bring hope, possibility and treatment options to these patients and families in need.

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