Investigations show that D/H isotope substitution stabilizes CAG repeats in the ATXN2 gene, suggesting new therapeutic avenues.
CAG repeats in the first exon of the ATXN2 gene play a key role in the development of a number of neurodegenerative diseases. Understanding the mechanisms underlying CAG tract expansions and the factors influencing them could lead to the development of new methods for the prevention and treatment of these diseases. It was established that a single D/H substitution of a hydrogen bond in the CAG tract increases its stability, thereby reducing the likelihood of formation of secondary structures that interfere with the reading of genetic information from the glutamine-coding region. CAA interruptions in the CAG tract in specific locations can have a similar, but weaker, stabilizing effect.
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Dorohova et al. (2026) studied this question.
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