Description:

As genome-wide sequencing shortens diagnostic odysseys, individuals are increasingly embarking on therapeutic odysseys. Proof-of-concept exists for antisense oligonucleotides (ASOs) as a genetic medicine customized for an individual’s specific genetic variant and/or ultra-rare condition. Questions about ASOs – in our laboratories and in our clinics – are increasingly common. Our presenters are Canadian members of the N=1 Collaborative (N1C) (n1collaborative.org/), a global initiative to standardize ultra-rare “n-of-1/few” therapy development for safe and equitable delivery to individuals with rare diseases. In this session, we will present the N1C VARIANT (Variant Assessments towards Eligibility for Antisense Oligonucleotide Treatment) guidelines (https://www.medrxiv.org/content/10.1101/2024.09.27.24314122v1; Am J Hum Genet, accepted). We will provide resources/tools that facilitate this variant triage process, work through specific real-world examples, and show data that a meaningful proportion of genetic diagnoses identified by genome-wide sequencing may be amenable to ASO treatment (https://www.medrxiv.org/content/10.1101/2025.02.10.25321921v1). We will discuss frequently asked questions, and specifically outline an approach to explaining why an ASO may not be feasible for a given patient. Last, we will critically review factors necessary for pre-clinical development and clinical administration, and the resource allocation, ethical, and equity concerns that shape this emerging field of genetics.

Objectives

At the end of the session, participants will be able to:

  • Identify variant- and disease-level factors that impact eligibility for current ASO techniques.
  • Discuss approaches to frequently asked questions by patients, families, and clinicians about ASO eligibility.
  • Determine enablers and barriers at an institution level to developing and/or administering individualized ASOs.

Target Audience: Clinical Geneticists, Genetic Counsellors, Trainees
CanMEDS Roles: Medical Expert (the integrating role), Communicator, Collaborator, Scholar, Professional

Speaker: David Cheerie, Amy Pan, MSc, CGC, Dr. Gregory Costain

Event Timeslots (1)

Day 2
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KC 101-103-105 - David Cheerie, Amy Pan, MSc, CGC, Dr. Gregory Costain