From Single Cells to Therapies: Unravelling Rare Neurological Disorders with Advanced Sequencing

Ruwani Dissanayake

Neurodevelopmental disorders (NDDs) represent a significant global health challenge, affecting millions of children worldwide{1}. These conditions, encompassing a wide range of neurological and psychiatric disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability, often manifest early in life. They can have profound and lasting impacts on individuals, their families, and society as a whole. Understanding the biological roots of these complex disorders is crucial for developing effective therapeutic interventions. In this quest, cutting-edge technologies like transcriptomics and proteomics are providing unprecedented insights into the molecular landscape of neurological conditions. These approaches, including advanced sequencing techniques, offer tremendous potential for identifying new treatment targets that may lead to improved outcomes for children with neurodevelopmental disorders.

Professor Russell Dale, an internationally renowned expert in paediatric neuroimmunology, is the Clinical Director of the Kids Neuroscience Centre and Head of the Children’s Hospital Westmead Clinical School. He oversees specialised clinics providing vital care for children with complex NDDs. Under his guidance, a team including Dr. Shrujna Patel, Dr. Velda X. Han, Dr. Brooke A. Keating, Dr. Hiroya Nishida, Dr. Jessica Hayes, Dr. Shekeeb S. Mohammad has made advancements in understanding the interaction between the nervous and immune systems in children. Their combined expertise is contributing to progress in neuroimmunology, intending to develop better diagnostics and treatments.

AGRF has collaborated closely with Professor Dale and Dr. Patel over the past several years, particularly in the rapidly evolving field of transcriptomics. Our support has been instrumental in offering end-to-end bulk RNA sequencing services and played a pivotal role in evaluating the HIVE™ single-cell RNA sequencing (scRNA-seq) technology, establishing an optimised pipeline for paediatric samples in collaboration with Professor Dale and Dr. Patel [2]. The partnership between Professor Dale's team and AGRF brings together clinical expertise and advanced genomic technologies, accelerating discoveries that have the potential to transform the lives of children with neurological disorders. “Single-cell RNA sequencing allows a remarkable opportunity to identify gene regulation changes in single cells- the statistical power of examining ~15,000 patient cells compared to ~15,000 control cells help us understand cellular dysregulation in disease states. When used longitudinally, scRNA-seq can also help us visualise ‘how drugs work’ in an n=1 setting”, Prof. Dale says.

This powerful single-cell technique, when combined with proteomics, is already yielding exciting early insights that are reshaping our understanding of NDDs. For instance, Professor Dale's team recently published a ground-breaking work titled "Single-Cell RNA Sequencing in Incontinentia Pigmenti With Neonatal Encephalopathy Reveals Broad Immune Activation Moderated by Steroids {3]." This research highlights how scRNA-seq can provide valuable insights into immune pathways and therapeutic responses following steroid treatment for Incontinentia Pigmenti, a rare genetic condition primarily affecting females that causes abnormalities in the skin, eyes, teeth, and central nervous system [4].

“It's incredibly exciting to witness the progress Professor Dale's team is making,” says Ruwani Dissanayake, AGRF I&D Scientist. “Their work holds immense promise for translating discoveries into tangible benefits for children facing these challenging conditions. With so many experts working together and a shared goal of helping children, the future of NDD research is definitely looking up.”

References

1) WHO (2023). New report highlights neglected health needs of children with developmental disabilities. [online] www.who.int. Available at: https://www.who.int/news/item/15-09-2023-new-reports-highlights-neglected-health-needs-of-children-with-developmental-disabilities.

2) Dissanayake, R., Lau, P., Andrews, M., Keating, B.A., Han, V.X., Patel, S., Dale, R.C. and Moore, C. (2023). HIVE: A single cell technology to unravel the complexity of neutrophils [online] Honeycomb Biotechnologies, Inc. Available at: https://honeycomb.bio/resources/unraveling-the-complexity-of-neutrophils/

3) Mohammad, S.S., Han, V., Gloss, B., Keating, B., Nishida, H., Lau, X., Dissanayake, R., Patel, S. and Dale, R.C. (2025). Single-Cell RNA Sequencing in Incontinentia Pigmenti With Neonatal Encephalopathy Reveals Broad Immune Activation Moderated by Steroids. Neurology Neuroimmunology & Neuroinflammation, 12(3).  doi:https://doi.org/10.1212/nxi.0000000000200358

4) Yadlapati, S. and Tripathy, K. (2022). Incontinentia Pigmenti (Bloch Sulzberger Syndrome). [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK578194/