SGLT2 inhibitor treatment for dystrophic cardiomyopathy: an animal experiment of CRISPR/Cas9-generated rat model with Duchenne muscular dystrophy
K Kimura, Y Eiraku, R Tochinai, H Morita, N Takeda, T Nagamura-Inoue, K Nakanishi, K Hirose, M Daimon, N TakedaAbstract
Background
Duchenne muscular dystrophy (DMD) is an X-linked progressive myopathy caused by mutations in the dystrophin gene. The dystrophin deficiency causes progressive skeletal muscle dysfunction and life-threatening cardiomyopathy. Although heart failure is the leading cause of premature death, current medical treatment options are limited.
Aim
To clarify the efficacy and side effects of SGLT2 inhibitor as another medical option for dystrophic cardiomyopathy.
METHOD
Dapagliflozin 15 mg/kg/day was administrated orally for 16 weeks to CRISPR/Cas9-generated rat model with DMD.
Results
Echocardiography in Dapagliflozin group (n=7) showed trend toward larger left ventricular (LV) fractional shortening, tissue Doppler peak S’, and peak E’ waves (p=NS) than control group (n=5). Dapagliflozin group also showed lower heart weight (p<0.05) than control group. On the other hand, after 16 weeks medication, Dapagliflozin group showed lower body weight as well as weaker muscle strength (p<0.05).
Conclusion
SGLT2 inhibitor seems to be another treatment option for dystrophic cardiomyopathy. However, in the DMD treatment, careful attentions should be paid for risks of decrease in body weight and weakened muscle strength.