Table 5. [Dystrophin Restoration Therapies]. - GeneReviews®

Treatments	Mechanism of Action	Pros	Cons
ASOs (current US FDA-approved therapies): Eteplirsen (exon skip 51 amenable) Golodirsen (exon skip 53 amenable) Viltolarsen (exon skip 53 amenable) Casimersen (exon skip 45 amenable)	Restoration of reading frame by exon skipping in deletions	Currently approved treatments apply to ~30% of persons w/DMD; well tolerated; good safety profile	Weekly intravenous infusions; variant specific
Ataluren (approved by European Medicines Agency; not FDA approved)	Stop codon read-through strategy for nonsense variants	Orally administered; well tolerated; good safety profile	Variant specific
Gene transfer therapy (currently in clinical trials)	Micro-dystrophin constructs are inserted into AAV vectors to drive high levels of transgene expression & produce enough potentially functional micro-dystrophin.	Variant nonspecific; single intravenous administration	Cannot restore full-length dystrophin; durability of therapeutic response; safety concerns (possibility of integration into host genome & risk of mutagenesis)
CRISPR/Cas9-mediated gene editing (preclinical phase)	Programmable nucleases to correct a gene defect	Variant nonspecific	Off-target effects; safety & tolerability concerns

Treatments

Mechanism of Action

Pros

Cons

ASOs (current US FDA-approved therapies):

Eteplirsen (exon skip 51 amenable)
Golodirsen (exon skip 53 amenable)
Viltolarsen (exon skip 53 amenable)
Casimersen (exon skip 45 amenable)

Restoration of reading frame by exon skipping in deletions

Currently approved treatments apply to ~30% of persons w/DMD; well tolerated; good safety profile

Weekly intravenous infusions; variant specific

Ataluren (approved by European Medicines Agency; not FDA approved)

Stop codon read-through strategy for nonsense variants

Orally administered; well tolerated; good safety profile

Variant specific

Gene transfer therapy (currently in clinical trials)

Micro-dystrophin constructs are inserted into AAV vectors to drive high levels of transgene expression & produce enough potentially functional micro-dystrophin.

Variant nonspecific; single intravenous administration

Cannot restore full-length dystrophin; durability of therapeutic response; safety concerns (possibility of integration into host genome & risk of mutagenesis)

CRISPR/Cas9-mediated gene editing (preclinical phase)

Programmable nucleases to correct a gene defect

Variant nonspecific

Off-target effects; safety & tolerability concerns

From: Dystrophinopathies

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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