Promising Insights for Treating Barth Syndrome

barth syndrome
Study: Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome

Today, a paper in Nature Metabolism by researchers at the University of Pittsburgh outlines a potential new target and a small-molecule drug candidate for treating Barth syndrome, a rare, life-threatening genetic disease with devastating consequences that currently has no cure. Barth syndrome affects approximately 1 in every 300,000 to 400,000 babies born worldwide and is characterized by weak muscles and hearts, debilitating fatigue, and recurrent infections. The researchers at the University of Pittsburgh found that faulty mitochondria play a role in the disease and identified a molecular culprit that could be targeted to potentially reverse the disease course in the future.

In individuals without Barth syndrome, a lipid called cardiolipin (CL) undergoes a series of transformations, known as remodeling, within the mitochondria. However, in people with Barth syndrome, a crucial mitochondria-housed gene, called tafazzin (TAZ), is mutated, leading to halted CL remodeling and accumulation of harmful lipids. To conduct their latest investigation, the team utilized computational models and conducted in-vitro studies in both mouse myoblast cells and human heart-tissue samples from individuals with Barth syndrome.

We found that lyso-cardiolipin, an intermediate accumulating in mutant TAZ-deficient cells, interacts with the mitochondrial protein cytochrome c, converting it to a demon enzyme that oxidizes everything around it.”

Dr. Valerian Kagan, professor of environmental and occupational health

University of Pittsburgh School of Public Health

It appears that preventing excessive oxidation in TAZ-deficient cells is possible. The researchers demonstrated that a compound called imidazole-substituted oleic acid (IOA) could stop the formation of these complexes and enhance motor function and endurance in a fruit fly model of Barth syndrome. This finding could potentially lead to the correction of genetic tafazzin deficiency and the enhancement of mitochondrial function using small-molecule therapeutics in the future.

Rachel Paul is a Senior Medical Content Specialist. She has a Masters Degree in Pharmacy from Osmania University. She always has a keen interest in medical and health sciences. She expertly communicates and crafts latest informative and engaging medical and healthcare narratives with precision and clarity. She is proficient in researching, writing, editing, and proofreading medical content and blogs.

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