Investigation of a potential therapeutic role for N-oleoylethanolamide and N-linoleoylethanolamide using lymphoblasts deficient in Tafazzin

Abstract

Barth syndrome (BTHS) is a rare X-linked genetic disorder caused by mutations in the TAZ gene that encodes for a cardiolipin (CL) remodelling enzyme, Tafazzin. Due to an inability to remodel the fatty acyl chains on CL following de novo synthesis, patients with BTHS have reduced CL concentration and altered CL fatty acyl composition, leading to disorders, such as cardiomyopathy, skeletal myopathy, and cyclic neutropenia. Despite the advancements in BTHS research over the recent decade, clinical findings on BTHS immunity are still limited. This thesis aimed to examine the therapeutic potentials of two bioactive compounds, oleylethanolamine (OEA) and linoleoylethanolamine (LEA) in the treatment of BTHS lymphopenia, using lymphoblasts deficient in Tafazzin. Out of the two tested compounds, OEA was partially effective, while LEA had only minor effects and was thus discontinued from further experimentation. Additional studies focused on elucidating the direct mechanisms by which OEA exhibits positive effects on lymphoblast function. Results from this thesis provided novel insights on the therapeutic potential of OEA, and the potential importance of the mitochondria network as a target for treating BTHS.