Rare Neurodegenerative Disorder Patient Improves with Non-Profit's ASO Therapy

Researchers at the non-profit organization n-Lorem have discovered and developed a personalized antisense oligonucleotide (ASO) therapy to treat a rare neurological condition. A patient named Susannah, suffering from a progressive neurodegenerative disorder known as KIF1A-associated neurological disorder (KAND), has reported significant improvements after receiving this experimental treatment.

Susannah's condition, KAND, is caused by mutations in the KIF1A gene, which lead to a range of symptoms including motor impairments, developmental delays, and cognitive challenges. Currently, management of KAND focuses on symptom relief and quality of life improvements through supportive therapies such as speech and physical therapy. According to GlobalData’s Pharma Intelligence Center, there are no other therapies for KAND in clinical development.

Upon receiving her first dose of the personalized ASO medicine developed specifically for her genetic mutation, Susannah experienced a reduction in seizure frequency to fewer than 30 per week, and her condition stabilized. The management of her condition improved significantly, as she now experiences fewer daily falls, and many days she has no falls at all, compared to an average of 26.2 falls per day before treatment.

Additionally, data from a study published in Nature Medicine highlighted improvements in Susannah’s speech, attention, group interaction, and motor skills, while her cognitive abilities have remained stable. After 20 months of ASO treatment, Susannah has shown a favorable safety and tolerability profile.

ASO therapies utilize short, synthetic strands of nucleic acids to target and modify specific genes, aiming to reduce the production of harmful proteins or correct genetic defects. In Susannah’s case, the treatment targets and corrects the harmful version of the KIF1A gene.

n-Lorem, founded by the former CEO of Ionis Pharmaceuticals Stanley Crooke, aims to provide ASO therapies to patients diagnosed with ultra-rare diseases, typically affecting fewer than 30 individuals. Physicians can submit applications to n-Lorem, where the organization determines if the patient’s genetic mutation is suitable for ASO technology. To date, the organization has approved over 130 patient applications for various genetic mutations.

There has been a notable increase in the number of non-profits developing medications for rare diseases where the patient population is too small for commercial viability. For example, the Italian research charity Telethon Foundation manufactures and distributes Strimvelis, a gene therapy for the rare disease adenosine deaminase severe combined immunodeficiency (ADA-SCiD), after it was abandoned by a pharmaceutical company in 2022.

ASO therapies have garnered attention for their potential in treating rare diseases at the molecular level. Approved treatments for larger patient populations have also been developed, such as Biogen’s Spinraza (nusinersen) for spinal muscular atrophy, which achieved $610.5 million in sales in 2023.

In a statement, n-Lorem’s CEO Stanley Crooke expressed optimism regarding Susannah’s progress: “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.”

n-Lorem, which began its operations in 2020, is also conducting a study named KOALA (KIF1A Outcome Measures, Assessments, Longitudinal and Endpoints) to better understand the progression and variability of KAND symptoms over time.