Marcos J. Araúzo Bravo, leader of the group of Computational Biology and Systems Biomedicine, and Daniela Gerovska, a postdoctoral researcher from the same group have published an article showing for the first time the accumulation of extrachromosomal circular DNA (eccDNA) in Amyotrophic Lateral Sclerosis (ALS) neurodegeneration.

The published research is an unprecedented approach to couple episomal with genome-encoded variations in ALS. Given that the primal susceptibility to produce eccDNA originates from mutations in ALS-related genes that operate in genome protection, it might represent a yet unconsidered genomic factor on which clinically heterogeneous, but indiscriminate familial ALS (fALS) and sporadic ALS (sALS) converge. Prospective studies covering quantitative and qualitative eccDNA profiles in other neurodegenerative disorders will reveal whether eccDNA can qualify for a diagnostic or predictive biomarker role in f/sALS and even have a causal role in neurodegeneration. EccDNA might add up a new, heteroplasmy-like factor that drives somatic mosaicism and contributes to the genetic, and putatively clinical heterogeneity in ALS.

This study has been funded for Daniela Gerovska and Marcos J. Araúzo Bravo by the European Union’s Horizon 2020 research and innovation programme Future Emerging Technologies (FET-Open) under grant agreement No 899417 (CIRCULAR VISION: Circular DNA in diagnosis and disease models).

The study is in collaboration with researchers from the Department of Neurology, Jena University Hospital (Germany), and the Department of Biology, University of Copenhagen (Denmark); and it has been published in the journal Cell & Bioscience.

A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1^G93A model of ALS. Daniela Gerovska, Julie B. Noer, Yating Qin, Quratul Ain, Donjetë Januzi, Matthias Schwab, Otto W. Witte, Marcos J. Araúzo-Bravo & Alexandra Kretz. Cell & Bioscience 13, 170 (2023). https://doi.org/10.1186/s13578-023-01116-1