Undisclosed non-coding RNA (Hypertrophic Cardiomyopathy)

The undisclosed non-coding RNA implicated in hypertrophic cardiomyopathy (HCM) refers to a novel regulatory element, likely a long non-coding RNA (lncRNA), currently being pursued by biotechnology companies such as Tenaya Therapeutics and Haya Therapeutics (Tenaya Therapeutics, 2024; Haya Therapeutics, 2024). These ncRNAs act as master regulators of the cardiac hypertrophic gene program, coordinating the expression of multiple genes involved in sarcomere assembly, calcium handling, and myocardial fibrosis (Thum, 2014). In the context of HCM, these specific transcripts are typically upregulated, driving the pathological thickening of the heart walls and leading to impaired diastolic function (Viereck et al., 2016). The therapeutic approach involves using small molecules or antisense oligonucleotides to bind and inhibit the function of the ncRNA, thereby restoring a healthy gene expression profile. This strategy is particularly attractive because it allows for the modulation of pathways that were previously considered undruggable by traditional protein-targeting therapies. By targeting a central regulator, these therapies aim to provide a more comprehensive disease-modifying effect than agents targeting single downstream proteins. Current development is in the discovery and preclinical stages, with a focus on both genetic and non-genetic forms of the disease. Successful modulation of this target is expected to reduce cardiac hypertrophy, improve heart failure symptoms, and prevent disease progression in HCM patients.

Other names

Novel lncRNA target for HCMTenaya HCM small molecule targetPro-hypertrophic non-coding RNACardiac hypertrophy-associated transcript (CHAST) candidateUndisclosed lncRNA target (Haya Therapeutics)

Small molecule or antisense-mediated inhibition of a pro-hypertrophic non-coding RNA to normalize the cardiac gene expression profile and reduce pathological remodeling.