AIMS: Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to 
dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected 
patients lose ambulation by age 12 and usually die in the second to third 
decades of life from cardiac and respiratory failure. Symptomatic treatment 
includes the use of anti-inflammatory corticosteroids, which are associated with 
side effects including weight gain, osteoporosis, and increased risk of 
cardiovascular disease. Novel treatment options include blockade of the 
renin-angiotensin-aldosterone system, because angiotensin as well as aldosterone 
contribute to persistent inflammation and fibrosis, and aldosterone blockade 
represents an efficacious anti-fibrotic approach in cardiac failure. Recent 
preclinical findings enabled successful clinical testing of a combination of 
steroidal mineralocorticoid receptor antagonists (MRAs) and angiotensin 
converting enzyme inhibitors in DMD boys. The efficacy of MRAs alone on 
dystrophic skeletal muscle and heart has not been investigated. Here, we tested 
efficacy of the novel non-steroidal MRA finerenone as a monotherapy in a 
preclinical DMD model.
METHODS AND RESULTS: The dystrophin-deficient, utrophin haploinsufficient mouse 
model of DMD was treated with finerenone and compared with untreated dystrophic 
and wild-type controls. Grip strength, electrocardiography, cardiac magnetic 
resonance imaging, muscle force measurements, histological quantification, and 
gene expression studies were performed. Finerenone treatment alone resulted in 
significant improvements in clinically relevant functional parameters in both 
skeletal muscle and heart. Normalized grip strength in rested dystrophic mice 
treated with finerenone (40.3 ± 1.0 mN/g) was significantly higher (P = 0.0182) 
compared with untreated dystrophic mice (35.2 ± 1.5 mN/g). Fatigued 
finerenone-treated dystrophic mice showed an even greater relative improvement 
(P = 0.0003) in normalized grip strength (37.5 ± 1.1 mN/g) compared with 
untreated mice (29.7 ± 1.1 mN/g). Finerenone treatment also led to significantly 
lower (P = 0.0075) susceptibility to limb muscle damage characteristic of DMD 
measured during a contraction-induced injury protocol. Normalized limb muscle 
force after five lengthening contractions resulted in retention of 71 ± 7% of 
baseline force in finerenone-treated compared with only 51 ± 4% in untreated 
dystrophic mice. Finerenone treatment also prevented significant reductions in 
myocardial strain rate (P = 0.0409), the earliest sign of DMD cardiomyopathy. 
Moreover, treatment with finerenone led to very specific cardiac gene expression 
changes in clock genes that might modify cardiac pathophysiology in this DMD 
model.
CONCLUSIONS: Finerenone administered as a monotherapy is disease modifying for 
both skeletal muscle and heart in a preclinical DMD model. These findings 
support further evaluation of finerenone in DMD clinical trials.