Journal Article

DZNE-2022-00621

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Preparing n-of-1 Antisense Oligonucleotide Treatments for Rare Neurological Diseases in Europe: Genetic, Regulatory, and Ethical Perspectives.

Synofzik, M. (First author)DZNE* ; van Roon-Mom, W. M. C. ; Marckmann, G. ; van Duyvenvoorde, H. A. ; Graessner, H. ; Schüle, R.DZNE* ; Aartsma-Rus, A.

2022
Liebert New Rochelle, NY

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Please use a persistent id in citations: doi:10.1089/nat.2021.0039

Abstract: Antisense oligonucleotide (ASO) therapies present a promising disease-modifying treatment approach for rare neurological diseases (RNDs). However, the current focus is on 'more common' RNDs, leaving a large share of RND patients still without prospect of disease-modifying treatments. In response to this gap, n-of-1 ASO treatment approaches are targeting ultrarare or even private variants. While highly attractive, this emerging, academia-driven field of ultimately individualized precision medicine is in need of systematic guidance and standards, which will allow global scaling of this approach. We provide here genetic, regulatory, and ethical perspectives for preparing n-of-1 ASO treatments and research programs, with a specific focus on the European context. By example of splice modulating ASOs, we outline genetic criteria for variant prioritization, chart the regulatory field of n-of-1 ASO treatment development in Europe, and propose an ethically informed classification for n-of-1 ASO treatment strategies and level of outcome assessments. To accommodate the ethical requirements of both individual patient benefit and knowledge gain, we propose a stronger integration of patient care and clinical research when developing novel n-of-1 ASO treatments: each single trial of therapy should inherently be driven to generate generalizable knowledge, be registered in a ASO treatment registry, and include assessment of generic outcomes, which allow aggregated analysis across n-of-1 trials of therapy.

Keyword(s): Europe (MeSH) ; Humans (MeSH) ; Oligonucleotides (MeSH) ; Oligonucleotides, Antisense: genetics (MeSH) ; Oligonucleotides, Antisense: therapeutic use (MeSH) ; antisense oligonucleotides ; ethics ; n-of-1 ; policy ; rare diseases ; rare neurological diseases ; regulatory ; Oligonucleotides ; Oligonucleotides, Antisense

Note: (CC BY)

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser 1)
2. Functional Neurogeriatrics (AG Maetzler)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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