Precision Antisense Oligonucleotide Therapy Amenability for Infantile Genetic Epilepsies - Summary - MDSpire
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Feasibility of Precision Antisense Oligonucleotide Treatment for Genetic Epilepsies in Infants

  • By

  • Emma Sherrill

  • David Cheerie

  • Cara J. Beck

  • Ella F. Whittle

  • Yasin Shafi

  • Natalie J. Chandler

  • John Christodoulou

  • Jerusalem Daniel

  • Jane Hassell

  • Maria Lachgar-Ruiz

  • Sarah Mulhern

  • Elizabeth Scotchman

  • Jashanpreet Sidhu

  • Celine Florentia Tedja

  • Lyn S. Chitty

  • J. Helen Cross

  • Ingrid E. Scheffer

  • Haiyan Zhou

  • Timothy W. Yu

  • Vann Chau

  • Sarah E. M. Stephenson

  • Annapurna Poduri

  • Katherine B. Howell

  • Amy McTague

  • Gregory Costain

  • Alissa M. D’Gama

  • Gene-STEPS Study Group

  • Joanna Cobb

  • Anna J S Griffiths

  • Edward J Higgenbotham

  • Puneet Jain

  • Nicole S Y Liang

  • Sebastian Lunke

  • Christian R Marshall

  • Catherine Marx

  • Lyndsey McRae

  • Jimmy N H Nguyen

  • Wanqing Shao

  • Beth R Sheidley

  • Lacey Smith

  • Zornitza Stark

  • Susan M White

  • June 1, 2026

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Objective:

To determine the proportion of genetically diagnosed infants with epilepsy who are amenable to antisense oligonucleotide (ASO) therapy approaches.

Approach:
  • Study Design: Cohort study involving rapid genome sequencing and ASO assessment in infants with new-onset unexplained epilepsy or complex febrile seizures.
  • Participants: 160 genetically diagnosed infants enrolled from September 2021 to March 2025.
  • Assessment Methodology: Variants classified using N1C guidelines and splice-switching framework by independent assessors.
Key Findings:
  • 15 of 152 variants (10%) were classified as eligible for ASO therapy by N1C guidelines.
  • 24 unique variants from 25 infants (16%) were found amenable to ASO therapies.
  • 68% of infants with amenable variants could be considered for ASO therapies currently.
Interpretation:

The findings suggest that a significant proportion of genetically diagnosed infants with epilepsy may benefit from ASO therapies. The identification of amenable variants highlights the potential for targeted treatment approaches in this population. The use of rapid genome sequencing is crucial in expediting the identification of candidates for such therapies, which can lead to timely interventions.

Limitations:
  • 56 variants classified as unable to assess due to lack of functional evidence.
  • Need for rapid genome sequencing and variant assessment to identify therapy candidates.
Conclusion:

The study demonstrates the feasibility of ASO therapy for a subset of infants with genetic epilepsies, emphasizing the importance of precision medicine in improving treatment outcomes for this vulnerable population. Further research is needed to expand the understanding of the functional implications of variants and to refine selection criteria for ASO therapies. ---

Original Source(s)

Precision Antisense Oligonucleotide Therapy Amenability for Infantile Genetic Epilepsies

  • by Emma Sherrill, David Cheerie, Cara J. Beck, Ella F. Whittle, Yasin Shafi, Natalie J. Chandler, John Christodoulou, Jerusalem Daniel, Jane Hassell, Maria Lachgar-Ruiz, Sarah Mulhern, Elizabeth Scotchman, Jashanpreet Sidhu, Celine Florentia Tedja, Lyn S. Chitty, J. Helen Cross, Ingrid E. Scheffer, Haiyan Zhou, Timothy W. Yu, Vann Chau, Sarah E. M. Stephenson, Annapurna Poduri, Katherine B. Howell, Amy McTague, Gregory Costain, Alissa M. D’Gama, Gene-STEPS Study Group, Joanna Cobb, Anna J S Griffiths, Edward J Higgenbotham, Puneet Jain, Nicole S Y Liang, Sebastian Lunke, Christian R Marshall, Catherine Marx, Lyndsey McRae, Jimmy N H Nguyen, Wanqing Shao, Beth R Sheidley, Lacey Smith, Zornitza Stark, Susan M White

  • June 1, 2026

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