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.