n-Lorem discovered, developed and provided an allele selective ASO for each Patient

n-Lorem, a nonprofit foundation that discovers develops and provides personalized experimental antisense oligonucleotide (ASO) medicines to patients with nano-rare mutations (1-30 known worldwide) for free, for life, announced today the publication in Nature Medicine of treatment results from two modified-cross-over design clinical trials of two allele-selective ASOs, one for each patient with a pathogenic mutation in an essential sodium channel encoded by the SCN2A gene. In both cases, the safety and tolerability profile was excellent with no ASO-related adverse events or serious adverse events.

The studies were conducted in conjunction with principal investigators, Drs. Olivia Kim-McManus at the University of California San Diego and Rady Children’s Institute for Genomic Medicine and Elizabeth Berry-Kravis at Rush University Medical Center. The study details two first-in-human, single-patient clinical trials using highly selective, allele-selective and personalized ASO medicines designed specifically for each child. Allele-selective ASOs selectively reduce the mutant mRNA and protein while sparing the normal RNA and protein, which is required to treat heterozygous toxic gain-of-function mutations in essential gene products. ASO technology is the only technology that can routinely provide medicines with such precise selectivity.

“We are thrilled with the benefits we are observing in ASO-treated patients. Like these two patients with mutations in the SCN2A gene, many of our patients begin treatment with advanced disease and many have missed key development milestones. It is remarkable to me that we are observing the recovery of milestones and the achievement of milestones never achieved in our patients,” said Dr. Stanley Crooke, CEO of n-Lorem. “Each nano-rare patient deserves to have hope of a better future. Our commitment is to assure that our patients are treated as safely as possible, which is exactly what we are doing. The excellent safety and tolerability profile that we are observing in more than 50 patients treated is a result of the quality of our processes and the experience that informs our decision making.”

“As we continue to gain more experience in patients treated with bespoke ASO medicines, these data are reshaping what we believe is possible for neurodevelopmental disorders,” commented Elizabeth Berry-Kravis, M.D., Ph.D., Professor of Pediatrics and Neurological Sciences, Rush University Medical Center in Chicago. “Many of our patients begin treatment with advanced disease and significant developmental impairment, yet in some cases, we are observing the achievement of milestones never previously reached. These findings suggest that developmental trajectories may be more dynamic than we have traditionally believed, and that targeted therapies like ASOs may offer the opportunity to meaningfully change that trajectory.”

SCN2A variants are among the most common genetic causes of severe early-life epilepsies, often presenting with uncontrolled seizures in the first days of life and leading to profound developmental impairment.​

"Antisense oligonucleotides and gene therapies are translational platforms, revealing the biology of disease in real time while reshaping it. In doing so, they offer a path to transformative care for monogenic neurologic disorders, where a precise intervention early in life—especially in infants and children—may change disease trajectory toward the potential for improved development, function, and future," commented Olivia Kim-McManus, M.D., 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.

The two patients presented with severe seizures unresponsive to standard treatments, severe motor dysfunction, severe developmental delays and autistic behavior. Once on treatment, both patients experienced significant reductions in seizures, substantial improvements in control of movements, improved autistic symptoms, improvement in rate of development in some areas, acquisition of new skills such as walking independently and improved quality of life based on pre-defined endpoints and standard measures. One patient demonstrated improvements in autonomic dysfunction manifested by improved gastrointestinal function. Both patients have been treated for more than two years and no ASO-related adverse events have been reported.

“SCN2A encodes an essential protein and represents a significant challenge to discover an ASO that is selective to only the mutant RNA and mutant SCN2A protein. Not only did we succeed at making a highly selective and potent ASO, we discovered two different highly selective and potent ASOs. ASO selectivity is extremely important to ensure the upmost safety when treating these patients and represents an important advancement in ASO therapeutics,” continued Dr. Crooke. “At n-Lorem, approximately 60% of accepted patients require this type of allele-selective approach and we have become the leading experts in creating these types of medicines. Including these two patients, we have treated 15 patients with allele-selective ASOs, almost half of these patients for more than a year.”

The Nature Medicine article titled “Individualized Antisense Oligonucleotides for SCN2A Related Developmental Epileptic Encephalopathy,” highlights n-Lorem’s mission to provide free, lifetime treatments to patients with nano-rare mutations that result in life-threatening conditions.

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 needy patients and families.

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 440 applications for treatment with more than 240 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 X, 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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