Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

Abstract

In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10-18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated "by patient" (HR 0.33, p = 0.0187) and for "all BAEs" (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics.

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

“…In a phase II clinical trial, Idebenone showed positive effects on functional cardiac and respiratory parameters in DMD patients [52]. A phase III clinical trial showed reduction of loss of respiratory functions in DMD patients, even in the absence of glucocorticoid treatment [53,54].…”

Measurement of Respiratory Function Decline in Patients with Duchenne Muscular Dystrophy: A Conjoint Analysis

“…This gap has been fixed by the introduction of a different molecule: idebenone, a short-chain benzoquinone characterized by potent antioxidant activity and with the ability to stimulate mitochondrial electron flux and cellular energy production [16,17]. It has been shown in multicenter clinical trials that idebenone is able to slow the decline of pulmonary function of DMD patients, with a consequent reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics [6,7,18,19].…”

“…However, in clinical practice, loss of respiratory function continues to be a predominant cause of early morbidity and mortality in DMD patients [6]. Therefore, prevention of these complications and institution of early treatment as necessary now represent major goals [7]. To this end, tools able to stratify patients on the basis of their risk to develop respiratory complications would be a landmark improvement in the management of DMD.…”

Therapies that are available and under development for Duchenne muscular dystrophy: What about lung function?

“…We have identified 19 studies fulfilling our selection criteria [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] ( Figure 1): nine studies exploring the effect of steroids on pulmonary function, [17][18][19][20][21][22][23][24][25] six studies exploring the effect of idebenone (one study explored the effect of both steroids and idebenone), 19,[26][27][28][29][30] three studies about eteplirsen, [31][32][33] one study about ataluren, 34 and one study about stem-cell therapy 35 (Tables 1-3).…”