Abstract
BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe lethal X-linked monogenic recessive congenital muscular dystrophy caused by various types of mutations in the dystrophin gene (DG). It is one of the most common human genetic diseases and the most common type of muscular dystrophy, in part because DG is one of the largest protein-coding genes in the human genome with a relatively high risk of being affected by a large palette of mutations. Long-term corticosteroid therapy (LTCT) with deflazacort started at age 4 is the most accessible and used pharmacological therapy for DMD in Romania. "Asea(®) redox supplement" (ARS) is an approved dietary supplement in the European Union. Several studies have shown that it is a very potent selective NRF2 activator, and thus a very potent, albeit indirect, antioxidant, with no toxicity up to high doses, in contrast to LTCT. CASE SUMMARY: This paper presents a 3-case series on the effects of ARS in a 4-year-old, 5-year-old and 3-year-old boy all with DMD from Bucharest or Slobozia (Romania). This is the first report of this type worldwide. The parents of these boys had refused LTCT. They were treated with relatively high doses of ARS (3-7 mL/kg/day). For two patients, ARS was administered in combination with medium doses of L-carnitine and omega-3 fatty acids for various intellectual disabilities. Periodic consults and assessments for rhabdomyolysis, medullar and liver toxicity markers (blood count, gamma-glutamyl transferase, aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, creatine kinase, creatine kinase-MB and serum myoglobin) were performed. In vitro studies showed that ARS is a very potent and selective NRF2 activator, and thus a very potent indirect antioxidant. The in vivo studies also support this main pharmacological mechanism of ARS, with no toxicity at high doses, in contrast with much more toxic corticosteroids which are often refused by parents for their children with DMD. Although they were three distinct ages and carried three distinct DG mutations, from the first months of ARS-based treatment, the children responded similarly to ARS. The rhabdomyolysis markers, which were initially very high, significantly dropped, and there was no evidence for medullar and/or hepatic toxicity in any of the 3 patients. CONCLUSIONS: ARS has significant indirect antioxidant effects via NRF2 and deserves extensive trials in children with DMD, as an adjuvant to corticoids or as a substitute in DMD patients who refuse corticoids. Future trials should also focus on ARS as an adjuvant in many types of acute/chronic infectious/non-infectious diseases where cellular oxidative stress is involved.