Children's Mercy Kansas City has made a significant advancement in treating rare genetic diseases using personalized antisense oligonucleotides (ASOs). This innovative approach has yielded promising results in preclinical evaluations, offering hope for patients with previously untreatable conditions. The method validates personalized therapies in just eight weeks, significantly faster and more cost-effective than the industry average.
The study, titled "Rapid and scalable personalized ASO screening in patient-derived organoids," was published in the journal Nature.
While many laboratories currently generate patient-derived induced pluripotent stem cells (iPSCs), this process can take up to a year and cost between $5,000 and $10,000 per patient. The new method requires only a small number of patient blood cells, generating iPSCs in two to three weeks at a cost of less than $500 per patient.
The research team utilized these patient-derived iPSCs to grow patient-specific organoids—three-dimensional cell models that replicate organ development and function. These organoids serve as powerful tools for understanding disease biology and developing patient-specific therapeutics.
Scott Younger, Ph.D., Director of Disease Gene Engineering at the Genomic Medicine Center and leader of The Younger Laboratory, stated, "The team can generate iPSCs and organoid models for many patients in parallel, leading to an accelerated evaluation of therapeutic interventions. Instead of waiting over a year for cell models to be generated, a family could go from blood draw to diagnosis and/or treatment recommendation in a month or two."
The Children's Mercy Genomic Medicine Center validated the process using samples from three patients with Duchenne muscular dystrophy enrolled in its Genetic Answers for Kids (GA4K) program. They successfully restored dystrophin protein expression and function in patient-derived organoids using an FDA-approved ASO for one patient and customized ASOs for the other two.
Steve Leeder, PharmD, Ph.D., interim executive director of the Children's Mercy Research Institute, noted, "Patient-derived organoid models have the potential to be widely used in creating cellular systems for investigating disorders involving the heart, kidney, liver, and other tissues. They can also help identify effective medications for specific patients."
The research team anticipates that this method will be adopted by other institutions to provide faster, better care for rare disease patients globally. Dr. Younger emphasized, "The methods and protocols generated in this study are accessible and can be implemented in any standard research laboratory without the need for specialized equipment or high-cost reagents. The widespread ability to generate patient-derived cellular systems will significantly enhance our understanding of disease mechanisms and therapeutic options for many rare diseases."