Urinary prostaglandin metabolites as Duchenne muscular dystrophy progression markers

Patients with Duchenne muscular dystrophy (DMD) exhibit increased prostaglandin D₂ (PGD₂) expression in necrotic muscle and increased PGD₂ metabolites in their urine. In mouse models, inhibiting PGD₂ production suppresses muscle necrosis, suggesting a possible intervention through PGD₂-mediated activities.

We investigated the involvement of PGD₂ and its potential use as a marker of pathological progression in DMD.

Sixty-one male children with DMD and thirty-five age-matched controls were enrolled in the study. DMD patients were divided into "ambulant" and "non-ambulant" groups, which were further subdivided into "steroid" and "non-steroid" therapy groups. Levels of the PGD₂ metabolite tetranor-PGDM (t-PGDM) and creatinine were measured in both spot and 24-hour urine samples, with comparisons between groups made according to geometric mean values.

DMD patients had significantly higher levels of creatinine-corrected t-PGDM in spot urine samples as compared with the control group. Additionally, both ambulant and non-ambulant DMD groups had significantly higher levels of t-PGDM as compared with controls, with no significant difference in t-PGDM levels observed between steroid and non-steroid groups. Moreover, total creatinine excretion in 24-hour urine samples was significantly lower in DMD patients as compared with controls, and although DMD patients had lower muscle mass than controls, their overall levels of t-PGDM did not differ significantly from those in the non-ambulant and control groups.

PGD₂ might help explain the progression and symptomatic presentations (e.g., ambulatory difficulty) associated with DMD, suggesting it as a useful pathological marker and use of a selective PGD₂ inhibitor as a potential treatment modality.