For Every Patient Their Own Drug – Image for illustrative purposes only (Image credits: Unsplash)
More than 50 patients worldwide now receive experimental drugs designed exclusively for them, targeting genetic mutations so rare they affect only one to 30 individuals globally. This approach, known as n-of-1 medicine, emerged from decades of persistence by physician and drug developer Stan Crooke. At the n-Lorem Foundation, which he founded, antisense oligonucleotides – or ASOs – offer a rapid path to personalized therapies for those who slip through the standard medical system’s gaps.
A Lifetime Dedicated to Drug Innovation
Stan Crooke’s path to pioneering individualized treatments began in a challenging Indianapolis childhood in 1945. Raised amid family struggles, including his mother’s addictions and health issues, he supported his household through early jobs like a paper route and pharmacy work. Academic hurdles marked his youth: He left Purdue University’s engineering program after struggling but earned a master’s in pharmacology from Butler University.
His breakthrough came at Baylor College of Medicine during an M.D.-Ph.D. program. There, as a student, Crooke witnessed a young man’s terminal testicular cancer diagnosis. The team offered an experimental Japanese drug, bleomycin, which intrigued him with its novel structure and unknown mechanism. This moment shifted his focus. He realized that developing effective drugs could impact more lives than direct patient care alone.
Crooke joined Bristol Labs and later rose through pharmaceutical ranks, always prioritizing patient needs amid his wife’s illness and family demands.
Mastering Antisense Technology
Crooke encountered antisense technology in 1987 at a symposium while leading research and development at SmithKline. Two 1978 studies had shown synthetic DNA strands could block viral protein production in cells by binding messenger RNA. The potential for broader medical applications captivated him.
After leaving SmithKline in 1988, he founded what became Ionis Pharmaceuticals in 1989. Over three decades, the company refined ASOs, achieving early approvals for conditions like CMV retinitis and homozygous familial hypercholesterolemia, though those drugs later discontinued due to low demand. Setbacks included costly trial failures and financial losses topping $1.1 billion by 2015.
Triumph arrived in 2016 with Spinraza, approved for spinal muscular atrophy. This ASO boosts protein production from a backup gene, transforming outcomes for children who once faced early death. By late 2025, it reached over 14,000 patients across more than 70 countries. Crooke credited 25 years of work on RNA stability, delivery, and safety. He stepped down in 2021 at age 76.
From Platform to Personalized Medicine
The idea for n-Lorem crystallized around 2018 when parents of boys with SCN2A mutations – disrupting brain cell communication – approached Ionis for custom ASOs. Crooke recognized the financial impossibility for for-profit companies but saw ASO efficiency allowed quick design. A moral imperative drove him forward.
Launching in 2020, n-Lorem anticipated five applicants but received 53 initially, surging to over 400 by late 2025. The foundation created ASOs for 216 patients and dosed more than 50. Crooke and his wife invested $10 million; Ionis and Biogen provided early support. Operations cost nearly $16 million in 2024, funded by donations, grants, and partnerships. Families cover administration, often via insurance or trials.
Crooke described the work as returning to patient care: “very much more like seeing patients again.” A colleague noted his kinder demeanor now.
Real Lives Transformed, With Caution
Susannah, diagnosed at 1.5 years with a KIF1A mutation causing neurodegeneration, endured 100-290 daily “behavioral arrests.” Starting n-Lorem treatment in November 2022, higher doses reduced episodes to 30 per week. She gained speech, mobility, and vision; now she stands and walks with aid after three years.
Other cases show promise and hurdles. Harlow, 5, received her first dose for a TUBB4A mutation in October 2025. Two 3-year-old girls with KCNT1 mutations faced brain swelling; one died after treatment withdrawal, while the other’s seizures dropped 66% after two years. Mila, treated with a custom ASO called Milasen for Batten disease, saw an 80% seizure reduction before passing in 2021 at age 10.
- Safety profiles remain mostly clean, though rare issues like fever or hydrocephalus appeared.
- Drug regulators increasingly consider benefits of bespoke therapies.
- Pioneer patients like Susannah guide future designs.
A New Era for the Medically Overlooked
n-Lorem bridges genomic discovery to treatment faster than traditional paths, which span 10-15 years and billions. Yet challenges persist: funding sustainability, regulatory navigation for single-patient trials, and long-term monitoring. Crooke, reflecting on his journey, emphasized responsibility: “I like being responsible. And when I had the chance to take care of a patient, I changed.”
This model signals a shift. For nano-rare patients, once deemed untreatable, custom ASOs offer not just hope but tangible progress – one precisely engineered drug at a time.