From made-to-order genetic therapies to model organisms engineered to be ‘patient avatars’, the technology exists right now to save patients with rare diseases.
Last October, Susannah Rosen, an 8-year-old girl with a devastating neurodegenerative genetic disease, took her first dose of a custom-made genetic medicine. What’s more, she got it at no cost, provided by the non-profit foundation n-Lorem. The drug isn’t gene therapy: it doesn’t change Susannah’s genome or undo her mutation. It’s an antisense oligonucleotide (ASO), a short sequence of modified DNA, designed to bind to a problematic mRNA transcript and stop production of the disease-causing protein.
Susannah joins a small but growing group of patients who have received treatments designed just for them, called ‘N of 1’ therapies. Personalized medicine seemed to be just around the corner for decades, but in 2018, the corner had finally been turned when a custom-designed ASO made its clinical debut at Boston Children’s Hospital.
Researchers there, led by Tim Yu, developed an ASO drug called milasen to treat a child — Mila — who had a one-of-a-kind genetic disorder. Incredibly, that drug was designed, manufactured and administered in less than a year1.
ASOs are only one approach to designing N-of-1 drugs; CRISPR gene editing, an inherently customizable tool, is moving successfully into the clinic, making it another promising candidate. Clinical trials underway for genetic diseases including sickle cell anemia and congenital blindness, though these are not ultra-rare conditions, nonetheless have demonstrated that the technique can be used safely in humans. Some people are pushing to apply personalized CRISPR therapies more broadly, but regulators remain cautious. Once gene editing is performed, it can’t be reversed if adverse events arise.