Temporal evolution of the heart failure phenotype in Barth syndrome and treatment with elamipretide

Area of Science:

• Genetics and Molecular Biology
• Cardiology
• Mitochondrial Biology

Background:

• Barth syndrome (BTHS) is a rare genetic disorder caused by pathogenic variants in the *TAFAZZIN* gene.
• This leads to reduced remodeled cardiolipin (CL), a critical phospholipid for mitochondrial function and structure.
• Most BTHS patients develop cardiomyopathy, initially dilated (DCM) and later potentially hypertrophic (HCM), resembling heart failure with preserved ejection fraction (HFpEF).

Purpose of the Study:

• To evaluate elamipretide as a therapeutic agent for Barth syndrome.
• To assess elamipretide's potential to improve mitochondrial function and cardiac health in BTHS patients.

Main Methods:

• Elamipretide targets the inner mitochondrial membrane, interacting with cardiolipin.
• Preclinical and clinical studies investigated its effects on mitochondrial function, structure, and bioenergetics.

Main Results:

• Elamipretide improves mitochondrial function and bioenergetics, including ATP synthesis.
• Studies indicate it ameliorates mitochondrial dysfunction, enhancing left ventricular relaxation.

Conclusions:

• Elamipretide's mechanism of action makes it suitable for treating adolescent and adult BTHS patients.
• It offers a potential therapeutic strategy for improving cardiac outcomes in Barth syndrome by addressing underlying mitochondrial defects.