A retrospective study in which we reviewed the hospital files of a subset of 7 patients with
Duchenne muscular dystrophy participating in the open-label phase I/II PRO051-02 study in Leuven. The objective of this study was to describe in detail the
injection site reactions in these children treated with
drisapersen (PRO-051), a 2'-O-methyl phosphorothioate
RNA antisense oligonucleotide, that induces exon 51 skipping in
Duchenne muscular dystrophy.
Antisense oligonucleotides, restoring the reading frame by skipping of exons, have become a potential treatment of
Duchenne muscular dystrophy and other monogenetic diseases.
Erythema followed by
hyperpigmentation,
fibrosis, and calcification were seen at the injection sites in all children. Ulcerations, which were difficult to heal, occurred in 5 of 7 children. Progression still occurred after switching to
intravenous administration of
drisapersen or even after stopping
therapy. Systemic reactions included a reversible
proteinuria and α1-microglobulinuria. Moreover,
hypotrichosis was a common feature.Conclusion: Subcutaneous administration of
drisapersen causes severe and progressive injection site effects. What is known: •
Antisense oligonucleotides offer the possibility to convert
Duchenne muscular dystrophy to the less severe Becker type. This can potentially be achieved by targeting and skipping specific exons of the
Duchenne muscular dystrophy gene to restore the disrupted reading frame and to induce the production of a semi functional
dystrophin protein. •
Drisapersen is such an
antisense oligonucleotides which can be administered subcutaneously. Its use has been tested extensively in the escalating dose pilot study (PRO051-02). What is new: • This report describes the
injection site reactions caused by this type of agent in detail which has never been done before. We therefore reviewed the hospital files of 7 patients with
Duchenne muscular dystrophy participating in the phase I/II open-label, escalating dose pilot study (PRO051-02) with
drisapersen. • Severe side effects starting with
erythema,
hyperpigmentation, and later
fibrosis, calcification, and difficult to treat ulcerations developed in all patients, and these continued to progress even after cessation of
drisapersen. We discuss some possible underlying mechanisms. The exact mechanism however is still not known.