Cardiac hypertrophy-associated transcript (CHAST) (CHAST)

Cardiac hypertrophy-associated transcript (CHAST) is a long non-coding RNA (lncRNA) that serves as a critical regulator of pathological cardiac remodeling and cardiomyocyte growth. It is significantly upregulated in the hearts of patients with aortic stenosis and in various animal models of pressure overload-induced heart failure. CHAST exerts its pro-hypertrophic effects by negatively regulating the expression of Pleckstrin homology domain-containing protein family M member 1 (PLEKHM1), a key protein involved in the regulation of autophagy; the resulting impairment of autophagic flux drives the progression of cardiac hypertrophy. CDR348T is a preclinical drug candidate developed by Cardior Pharmaceuticals (now part of Novo Nordisk) that utilizes antisense oligonucleotide technology to specifically target and inhibit CHAST. By silencing this lncRNA, CDR348T aims to restore normal autophagic processes and halt or reverse the development of hypertrophic cardiomyopathy, offering a potential restorative therapy for patients with limited treatment options.

Other names

Cardiac hypertrophy-associated transcriptLncRNA CHASTNon-coding RNA target of CDR348T

Antisense oligonucleotide-mediated knockdown of CHAST to restore cardiomyocyte autophagy and prevent pathological cardiac remodeling.