Animal experiment:

Mice[1]Male mdx or WT mice are used. Drug treatment protocols entail feeding individually housed mice a specialty control chow or chow containing either CAT-1041 or Edasalonexent (0.75% w/w) ad libitum starting at 4 weeks of age. Average drug consumption typically ranges between 0.75 and 1 mg/g body weight per day. The 24-hour plasma exposure at this dosage is 450ng hr/mL for Edasalonexent[1].

Edasalonexent is an orally bioavailable NF-κB inhibitor.

Edasalonexent is an orally administered small molecule in which salicylic acid and docosahexaenoic acid (DHA) are covalently conjugated through an ethylenediamine linker and that is designed to synergistically leverage the ability of both of these compounds to inhibit NF-κB. Edasalonexent significantly inhibits NF-κB p65-dependent inflammatory responses as well as downstream proinflammatory genes modulated by p65 in the golden retriever duchenne muscular dystrophy (DMD) model[2].

The treatment of mdx mice with Edasalonexent for 20 weeks results in reduced susceptibility of the extensor digitorum longus muscle to eccentric contraction-induced injury[1].

[1]. Hammers DW, et al. Disease-modifying effects of orally bioavailable NF-κB inhibitors in dystrophin-deficient muscle. JCI Insight. 2016 Dec 22;1(21):e90341. [2]. Donovan JM, et al. A Novel NF-κB Inhibitor, Edasalonexent (CAT-1004), in Development as a Disease-Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects. J Clin Pharmacol. 2017 May;57(5):627-639.