Temporal Evolution of the Heart Failure Phenotype in Barth Syndrome and Treatment with Elamipretide

Abstract

Barth syndrome (BTHS) is a rare genetic disorder caused by pathogenic variants in TAFAZZIN leading to reduced remodeled cardiolipin (CL), a phospholipid essential to mitochondrial function and structure. Cardiomyopathy presents in most patients with BTHS, typically appearing as dilated cardiomyopathy (DCM) in infancy and evolving to hypertrophic cardiomyopathy (HCM) resembling heart failure (HF) with preserved ejection fraction (HFpEF) in some patients ≥12 years. Elamipretide localizes to the inner mitochondrial membrane where it associates with CL, improving mitochondrial function, structure and bioenergetics, including ATP synthesis. Numerous preclinical and clinical studies in BTHS and other forms of HF have demonstrated that elamipretide improves left ventricular relaxation by ameliorating mitochondrial dysfunction, making it well suited for therapeutic use in adolescent and adult patients with BTHS.

Keywords: :

• Barth syndrome
• cardiolipin
• cardiomyopathy
• elamipretide
• mitochondria

Author contributions

All authors contributed equally to production of this review. All authors read and approved the final manuscript.

Financial & competing interests disclosure

HN Sabbah is a consultant to Stealth BioTherapeutics, Inc. and member of their Scientific Advisory Board. HN Sabbah also serves as a consultant to Novartis Corp, Impulse Dynamics, ViCardia, Inc. and Vascular Dynamics Inc. and has received research grant funding from Novartis and Impulse Dynamics. HJ Vernon receives clinical trial and research funding from Stealth BioTherapeutics, Needham (MA, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing and editing assistance, including preparation of a draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by JL Dermatis and JA Shiffer (Write On Time Medical Communications, LLC). Writing assistance was funded by Stealth BioTherapeutics.