Entering the era of precision medicine to treat amyotrophic lateral sclerosis

TY - JOUR

T1 - Entering the era of precision medicine to treat amyotrophic lateral sclerosis

AU - Theunissen, Frances

AU - Flynn, Loren

AU - Iacoangeli, Alfredo

AU - Al Khleifat, Ahmad

AU - Al-Chalabi, Ammar

AU - Giordano, James J.

AU - Strømme, Masha

AU - Akkari, P. Anthony

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/10/23

Y1 - 2025/10/23

N2 - With the disease modifying therapy Qalsody (tofersen) which targets the RNA product of the SOD1 gene, having been shown effective in amyotrophic lateral sclerosis (ALS), the present perspective seeks to explore progress towards the implementation of precision medicine principles in ALS drug development. We address the advances in our understanding of the complex genetic architecture of ALS, including the varying models of genetic contribution to disease, and the importance of understanding population genetics and genetic testing when considering patient selection for clinical studies. Additionally, we discuss the advances in long-read whole-genome sequencing technology and how this method can improve streamlined genetic testing and our understanding of the genetic heterogeneity in ALS. We highlight the recent advances in omics-data for understanding ALS patient sub-groups and how this knowledge should be applied to pre-clinical drug development in a proposed patient profiling workflow, particularly for gene targeted therapies. Finally, we summarise key ethical considerations that are pertinent to equitable care for patients, as we enter the era of precision medicine to treat ALS.

AB - With the disease modifying therapy Qalsody (tofersen) which targets the RNA product of the SOD1 gene, having been shown effective in amyotrophic lateral sclerosis (ALS), the present perspective seeks to explore progress towards the implementation of precision medicine principles in ALS drug development. We address the advances in our understanding of the complex genetic architecture of ALS, including the varying models of genetic contribution to disease, and the importance of understanding population genetics and genetic testing when considering patient selection for clinical studies. Additionally, we discuss the advances in long-read whole-genome sequencing technology and how this method can improve streamlined genetic testing and our understanding of the genetic heterogeneity in ALS. We highlight the recent advances in omics-data for understanding ALS patient sub-groups and how this knowledge should be applied to pre-clinical drug development in a proposed patient profiling workflow, particularly for gene targeted therapies. Finally, we summarise key ethical considerations that are pertinent to equitable care for patients, as we enter the era of precision medicine to treat ALS.

UR - https://www.scopus.com/pages/publications/105019536607

U2 - 10.1186/s13024-025-00890-5

DO - 10.1186/s13024-025-00890-5

M3 - Article

SN - 1750-1326

VL - 20

JO - Molecular Neurodegeneration

JF - Molecular Neurodegeneration

IS - 1

M1 - 111

ER -