TY  - JOUR
AU  - Jonker, Anneliene H
AU  - Tataru, Elena-Alexandra
AU  - Graessner, Holm
AU  - Dimmock, David
AU  - Jaffe, Adam
AU  - Baynam, Gareth
AU  - Davies, James
AU  - Mitkus, Shruti
AU  - Iliach, Oxana
AU  - Horgan, Rich
AU  - Augustine, Erika F
AU  - Bateman-House, Alison
AU  - Pasmooij, Anna Maria Gerdina
AU  - Yu, Tim
AU  - Synofzik, Matthis
AU  - Douville, Julie
AU  - Lapteva, Larissa
AU  - Brooks, Philip John
AU  - O'Connor, Daniel
AU  - Aartsma-Rus, Annemieke
TI  - The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap.
JO  - Nature reviews / Drug discovery
VL  - 24
IS  - 1
SN  - 1474-1776
CY  - London
PB  - Nature Publ. Group
M1  - DZNE-2025-00045
SP  - 40 - 56
PY  - 2025
AB  - In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed. We discuss why the traditional drug development and reimbursement pathway is not fit for purpose in this field, and outline the pragmatic, regulatory and ethical challenges this poses for future access to N-of-1 therapies. Finally, we provide a roadmap for N-of-1 individualized therapy development.
KW  - Single-Case Studies as Topic
KW  - Humans
KW  - Drug Development: methods
KW  - Precision Medicine: methods
KW  - Genetic Therapy: methods
KW  - Genetic Therapy: trends
KW  - Rare Diseases: drug therapy
KW  - Rare Diseases: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:39496921
DO  - DOI:10.1038/s41573-024-01059-3
UR  - https://pub.dzne.de/record/274064
ER  -