Protective effects of rimeporide on left ventricular function in golden retriever muscular dystrophy dogs

Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy

“…IGF1 has also been shown to have cardioprotective effect on hypertensive rats by inhibiting NHE-1 activity necrosis [ 40 ]. Such biomarker signature nicely correlates with the recent cardioprotective effect observed in GRMD dogs treated with Rimeporide [ 12 ].…”

“…The cardioprotective effects of NHE-1 inhibitors, including Rimeporide, have been extensively studied in various animal models of myocardial infarction and dystrophic cardiomyopathy including DMD. A recently completed study in Golden Retriever muscular dystrophy (GRMD) dogs has confirmed the cardioprotective role of Rimeporide after a treatment in a preventing setting [ 12 ]. Other preclinical experiments [ 13 , 14 ] have underlined the significance of myocardial necrosis, due to pH abnormalities as well as calcium and sodium imbalances in the pathophysiology of heart failure and have demonstrated the beneficial effects of NHE-1 inhibition using Rimeporide in preventing the deleterious effects of Ca2+ and Na + overload [ 14 ].…”

A muscle fatigue-like contractile decline was recapitulated using skeletal myotubes from Duchenne muscular dystrophy patient-derived iPSCs

“… 26 and Ghaleh et al. 27 BGP-15 ∼1–10 μM poly (ADP-ribose) polymerase inhibitor Kennedy et al. 28 idebenone ∼1–10 μM antioxidant Buyse et al.…”

“…There were also no effects reported for BGP-15 28 or rimeporide. 26,27 Although most screened compounds failed due to no or adverse effects, at least three compounds ameliorated contractile performance decline. Creatine supplementation has previously been shown to possess positive activities in the muscles of DMD patients.…”

Current Pharmacological Strategies for Duchenne Muscular Dystrophy

“…The intracellular Na + overload in muscles is accompanied with muscle edema, which plays a role in muscle degeneration ( Weber et al, 2012 ; Mijares et al, 2014 ). Rimeporide is an inhibitor of NHE-1 and shows anti-inflammatory and anti-fibrotic effects in mdx mice ( Ghaleh et al, 2020 ). The positive effects on several pharmacodynamic biomarkers, including IGFBP1 and IGFBP6, have been reported in the Phase 1b study of Rimeporide ( Gidaro et al, 2017 ; Previtali et al, 2020 ).…”