Custom Experimental Medicine Helps Teen with Rare Genetic Disorder Walk

Connor Dalby, a 17-year-old with a rare genetic mutation causing severe epilepsy, can now walk unassisted after receiving a tailor-made experimental drug. The treatment, developed by the n-Lorem Foundation, was designed specifically for his genetic profile. Dalby's seizures dropped by 90%, and his seizure-free days increased from zero to 46%. The results, published in Nature Medicine on July 21, come from two parallel clinical trials testing n-of-one therapies for mutations in the SCN2A gene. The other participant, a boy who was 9 at the start, saw a 26% reduction in seizures, though not statistically significant, and stopped a medication he needed since infancy. Both tolerated the drugs well with no serious adverse events. The therapy involves allele-selective antisense oligonucleotides (ASOs) that target the harmful copy of the gene while allowing the healthy one to function. Dalby's newfound ability to walk suggests continued brain plasticity, according to co-author Olivia Kim-McManus. The n-Lorem Foundation was founded by Stanley Crooke, former CEO of Ionis Pharmaceuticals, after parents of affected children approached him. Challenges remain in scaling such personalized treatments, as noted by Timothy Yu of Boston Children's Hospital.