DSP

Desmoplakin (DSP) cardiomyopathy is a genetic disease characterized by a distinct form of ACM and a certain form of dilated cardiomyopathy, which is caused by mutations in the desmoplakin or DSP protein. DSP is a structural protein critical for force transmission in heart muscle.

Unlike many forms of ACM that predominantly affect the right side of the heart, DSP cardiomyopathy frequently affects the left side of the heart. The exact prevalence of DSP cardiomyopathy is unknown but may be as high as 4% of all inherited dilated cardiomyopathies and 4% of ACM, impacting up to 35,000 individuals in the US.

LX2021 is a gene therapy candidate we are developing to deliver a functional copy of the gene encoding connexin 43 (Cx43), a critical gap junction protein in the heart. It is being developed to treat a group of inherited cardiac muscle disorders associated with a high risk of sudden cardiac death.

Cx43 is an integral protein component of gap junctions and functionally allows small molecules and ions to flow directly between cells to allow for electrical synchronization of muscle contraction. In individuals with heart disease, including heart failure, Cx43 is often relocalized in the lateral walls of myocardial cells. As a result, it is significantly reduced at cardiac muscle cell junctions, especially in ACM populations.

Restoring Cx43 protein to cardiac muscle cell-cell junctions can potentially treat multiple genetic causes of ACM because the cardiac loss of Cx43 is a molecular deficit generally observed in all ACM patient populations.