Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA

Friedreich’s ataxia (FRDA) is an autosomal recessive, multisystem disorder caused by mutations in the FXN gene, progressively affecting the nervous system, heart, and other organs.1 A recent study published in Molecular Therapy Nucleic Acids by Yameogo et al. describes a novel, intronic point mutation that disrupts canonical splicing and severely reduces FXN mRNA and frataxin protein levels.2 Using patient-derived cells, the authors demonstrated that antisense oligonucleotides (ASOs) targeting splicing regulatory elements effectively restore splicing deficits and increase frataxin expression.