Novel mitochondria-targeting peptides (MTPs) as therapeutic intervention in Barth syndrome

Mitochondria-targeting peptides (MTPs) as therapeutic intervention in Barth syndrome Barth syndrome (BTHS) is a serious X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. Although BTHS is a multisystem disorder, cardiomyopathy which may be accompanied by endocardial fibroelastosis (EFE) and/or left ventricular noncompaction (LVNC) is the most significant clinical manifestation of the disease. Despite the recently acquired knowledge about its impact on mitochondrial function, there remains a gap in our understanding of the molecular/metabolic processes that lead to Barth syndrome associated cardiomyopathy and as a result, there are no FDA approved therapies specific for Barth syndrome cardiac manifestations. In the absence of such therapies, improvement in the life expectancy and positive disease outcomes in Barth syndrome will likely remain elusive. Our proposal addresses the critical need to develop new effective treatment that address cardiolipin abnormalities, the fundamental defect underlying BTHS. Our proposal also has an educational (AREA) component significance. It is expected to stimulate research at Cleveland State University - an urban institution that provides baccalaureate and advanced degrees for underrepresented and multicultural students populations.