Individualized antisense oligonucleotide treatment eligibility of patients living with neurodevelopmental diseases.

Annemieke Aartsma-Rus; Claudio Melo de Gusmao; Scott Demarest; Willeke van Roon-Mom; Holm Graessner; Lynn Wein Bush; Charlotte Kogel; Timothy Wei-Wen Yu; Matthis Synofzik; Rebecca Schuele

doi:10.1016/j.xcrm.2026.102989

PubMed · 42594875

Individualized antisense oligonucleotide treatment eligibility of patients living with neurodevelopmental diseases.

Annemieke Aartsma-Rus·Claudio Melo de Gusmao·Scott Demarest·Willeke van Roon-Mom·Holm Graessner·Lynn Wein Bush·Charlotte Kogel·Timothy Wei-Wen Yu·Matthis Synofzik·Rebecca Schuele

View original source ↗Export metadata ↓

Abstract

With advances in genetic diagnostic tools, pathogenic variants in patients with genetic diseases are being identified at an accelerated pace. For a subset of these patients, individualized genetic interventions such as antisense oligonucleotides (ASOs) would address the disease cause. These individualized, or n-of-1, ASOs are currently being clinically applied in dozens of cases but mainly in patients with neurodegenerative diseases. For neurodevelopmental disorders, however, several questions arise: (1) Are they treatable? (2) What is the appropriate time window? (3) Does the treatment effect justify the burden and risks of treatment? In this consensus statement, we argue for the case to consider the development of individualized ASO treatment for individuals living with neurodevelopmental diseases and discuss which aspects need to be taken into consideration.

Explore related subjects

Humans Oligonucleotides, Antisense Neurodevelopmental Disorders Precision Medicine Genetic Therapy antisense oligonucleotide individualized treatment n-of-1 neurodevelopmental diseases Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Annemieke Aartsma-Rus, Claudio Melo de Gusmao, Scott Demarest, Willeke van Roon-Mom, Holm Graessner, Lynn Wein Bush, Charlotte Kogel, Timothy Wei-Wen Yu, Matthis Synofzik, Rebecca Schuele. 2026-08-13. Individualized antisense oligonucleotide treatment eligibility of patients living with neurodevelopmental diseases.. https://doi.org/10.1016/j.xcrm.2026.102989

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2027

Global Genomic Surveillance.

Global genomic surveillance has emerged as a foundational pillar of public health in the twenty-first century, enabling real-time tracking of pathogen evolution and informing outbreak response. This chapter examines the strategic architecture of global genomic surveillance, focusing on its application to arboviruses such as chikungunya virus (CHIKV). It explores the integration of genomic data with epidemiological, clinical, and environmental information within a One Health framework, while addressing critical challenges in governance, equity, and interoperability. The discussion covers the entire genomic surveillance workflow, from sample collection and sequencing to bioinformatic analysis and phylogenetic inference, and highlights the transformative role of artificial intelligence (AI) in predictive surveillance. By analyzing global initiatives, operational barriers, and emerging technologies, this chapter underscores the necessity of sustainable, equitable, and interoperable genomic systems to proactively address current and future infectious disease threats.

Humans↗

PubMed2027

Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.

CRISPR screens, such as expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), enable the simultaneous measurement of transcriptomes, gRNA identity, and cell-surface protein expression at single-cell resolution to systematically interrogate gene function. This platform provides a powerful and scalable experimental approach for validating disease-associated regulators identified by large-scale association studies and other computational methods, including network-based analyses of multi-omics data. Here, as an example application, we describe an ECCITE-seq framework to characterize the transcriptomic consequences of perturbing multiple neuronal key driver genes associated with Alzheimer's disease (AD) in human-induced pluripotent stem cell (hiPSC)-derived neurons. More broadly, by integrating customized pooled gRNA libraries with different CRISPR effectors across multiple cell types, this approach allows for the assessment of the regulatory impact of candidate genes implicated in development and disease processes.

Humans↗

PubMed2027

Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.

Aberrant three-dimensional genome organization is a hallmark of cancer, often driving oncogene activation through mechanisms such as enhancer hijacking. High-throughput chromosome conformation capture (Hi-C) maps these interactions on a genome-wide scale. Unlike earlier dilution-based methods, in situ Hi-C performs proximity ligation within intact nuclei, minimizing random ligation noise and enabling fine-scale structure detection. This chapter describes an optimized in situ Hi-C protocol tailored for cancer cell lines using MboI digestion and biotin-mediated pull-down to generate high-complexity libraries. We further outline a computational workflow that extends beyond standard topological mapping of compartments and topologically associating domains to identify cancer-specific aberrations. Specifically, we focus on detecting chromosomal rearrangements (structural variants) and characterizing the distinct circular topology of extrachromosomal DNA. This integrated experimental and analytical framework provides the necessary tools to dissect the spatial dysregulation underlying tumor evolution.

Humans↗