Stan Crooke, now 81, pioneered a new model for treating patients with ultra-rare genetic disorders: developing antisense oligonucleotide (ASO) drugs tailored to individual patients. After decades leading Ionis Pharmaceuticals through the development of Spinraza (a blockbuster ASO for spinal muscular atrophy approved in late 2016), Crooke left in mid-2021 to establish n-Lorem, a nonprofit providing bespoke drug therapy for patients with nano-rare mutations affecting only 1 to 30 people globally.
From Ionis to n-Lorem
Crooke’s transition to n-Lorem began when parents of children with mutations in the SCN2A gene—essential for brain cell communication—approached him around 2018. The boys were “desperately ill,” and the parents asked if Ionis could build an antisense drug targeting their children’s defective gene. Crooke explained it was not financially viable to make and sell a drug for a single patient in the traditional capitalist system, which requires 10 to 15 years and $2.6 billion to create a new therapy. However, he felt a “moral imperative” to try when he realized antisense technology had become “efficient enough that I could probably make them an ASO and give it to them.”
Scale and Impact
n-Lorem opened in 2020 and received 53 applications that first year—far more than the approximately five Crooke expected. By the end of 2025, the nonprofit had received more than 400 applications and decided it could create ASOs for 216 nano-rare mutations. The organization has dosed more than 50 patients with various nano-rare mutations—more than any other organization. In 2024, n-Lorem’s spending was nearly $16 million. Stan and Rosanne started by putting in $10 million of their own money, with Ionis and Biogen as founding donors.
Patient Success: Susannah’s Story
Susannah, the first n-Lorem patient dosed in November 2022, had a mutation in her KIF1A gene causing a rare neurodegenerative condition. When dosed, she was experiencing between 100 and 290 “behavioral arrests” per day—moments of unresponsive staring sometimes accompanied by eye rolling. When her dose reached 80 mg, her behavioral arrests dropped to 30 per week, her speech improved, and her quality-of-life score increased. After more than three years of treatment, Susannah can stand and walk with assistance, and her vision has improved. As a “pioneer patient,” every metric she generates helps inform treatment for others with KIF1A mutations and patients with ultra-rare diseases in general.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://nautil.us/for-every-patient-their-own-drug-1280433/