Preclinical evaluation of antisense oligonucleotide therapy in a mouse model of HNRNPH2-related neurodevelopmental disorder

HNRNPH2 (pathogenic variants XL — haploinsufficiency)

Preclinical evaluation of antisense oligonucleotide (ASO) therapy in a mouse model — sustained phenotypic correction

Variants in HNRNPH2 cause an X-linked neurodevelopmental disorder characterized by developmental delay, intellectual disability and motor disturbance. The authors evaluate for the first time an antisense oligonucleotide (ASO) therapeutic strategy in a mouse model of the syndrome. Results demonstrate sustained phenotypic correction with improvement of neurological and behavioural parameters. This study establishes preclinical proof of concept for a targeted therapy for this NDD.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Major preclinical study: first demonstration of phenotypic correction by ASO in HNRNPH2-related NDD. Publication in Science Translational Medicine confers high credibility. To watch for a potential phase I clinical trial transition. Reinforces the importance of early diagnosis in female carriers.

known gene +0; innovative preclinical ASO approach +2; mouse model with phenotypic correction +2; direct clinical impact (therapeutic avenue) +2; Science Translational Medicine +2