CRISPR/Cas9 Gene Editing for Transthyretin Cardiomyopathy

A new RNA therapy shows durable reductions in serum transthyretin protein levels in an early study involving 36 patients.

Amyloid transthyretin cardiomyopathy (ATTR-CM), caused by myocardial deposition of misfolded TTR proteins, is associated with substantial morbidity and mortality. Trials of TTR stabilizers or silencers have efficacy, but patients' outcomes are relatively poor even with treatment. In a single-arm, phase 1, manufacturer-sponsored trial (NCT04601051), researchers assessed interim 1-year outcomes among individuals with ATTR-CM who received the non–FDA-approved CRISPR-Cas9 gene editor nexiguran ziclumeran (nex-z). This novel therapeutic RNA is packaged in a lipid nanoparticle designed for uptake in hepatocytes, where TTR synthesis occurs.

The 36 participants (median age, 78; 97% men; 22% Black) had a confirmed diagnosis of either wild-type or var…

Reviewing Author

Frederick A. Masoudi, MD, MSPH, MACC, FAHA

Disclosures

Consultant/Advisory BoardBristol Myers Squibb; CPC Clinical Research

Grant/Research SupportNational Heart, Lung, and Blood Institute

Editorial BoardsUpToDate; American College of Cardiology Self-Assessment Program (SAP)

Leadership Positions in Professional SocietiesAmerican College of Cardiology (Chair, Innovations Committee)