The 2026 Barth Syndrome International Scientific, Medical & Family Conference was held at the Hyatt Regency Coconut Point, Bonita Springs, Florida, USA, from 19th to 25th July 2026 with scientific programming beginning 22nd July. This biennial event assembled researchers, clinicians, and affected community members for its first gathering since the U.S. FDA granted accelerated approval to elamipretide (Forzinity™; Mighty Therapeutics), the first therapy for Barth syndrome and first ever mitochondrially targeted therapy, in September 2025. Scientific sessions addressed: (1) emerging cardiolipin biology; (2) convergent identification of ABHD18 as a therapeutic target for correction of the cardiolipin phenotype; (3) advancing therapeutic strategies including AAV gene therapy, enzyme replacement therapy, and ABHD18 inhibition; (4) the elamipretide post-approval program, including the SPIBA-401 confirmatory trial; (5) natural history characterization covering infant outcomes, extra-cardiac manifestations, diaphragm weakness, neutropenia, and amino acid metabolism; (6) regulatory and drug development strategies in ultra-rare indications; and (7) international Centers of Expertise models and the launch of the BarthINSIGHTS registry. This report summarizes the key scientific advances, discussions, and future priorities as they relate to Barth syndrome biology, therapeutic development, and clinical care.
Pre-B-cell leukemia transcription factor 3 (PBX3) is a TALE homeodomain protein involved in neural development, but its function in oligodendrocyte (OL) differentiation has remained unexplored. Here, we show that PBX3 expression is dynamically regulated during OL lineage progression, with peak expression in the corpus callosum at P14, corresponding to the onset of active myelination. In cultured primary oligodendrocyte precursor cells (OPCs), PBX3 expression peaked at OL-1DIV, an early stage of in vitro differentiation. Using OL lineage-specific Pbx3 conditional knockout mice, we found that Pbx3 deletion reduced the density of SOX10+ OL lineage cells and CC1+ mature OLs in the corpus callosum at P14 and P27, accompanied by decreased MBP expression. Notably, these deficits were largely resolved by P50, indicating an age-dependent rather than absolute requirement for PBX3. EdU labeling revealed reduced OPC proliferation in Pbx3 cKO mice, though the Olig1-Cre driver used for conditional deletion is active in early neural progenitors, and thus contributions from reduced OPC specification or generation cannot be excluded. Consistently, siRNA-mediated Pbx3 knockdown in primary OPCs impaired differentiation and reduced MBP expression in vitro. Collectively, our findings identify PBX3 as a positive regulator of OL differentiation during early postnatal development, with a temporally restricted requirement, and provide insights into the transcriptional control of CNS myelination.
The regulation of transcriptional activity constitutes a primary layer of control over cellular function across diverse tissues and cell types. This regulatory transcriptional landscape is largely governed by epigenetic mechanisms, including DNA and histone modifications, the dynamic activity of epigenetic “writers” and “erasers,” and the influence of small regulatory molecules such as microRNAs (miRNAs). miRNAs are small non-coding RNA molecules that play critical roles in transcriptional and post-transcriptional gene regulation. By modulating the expression of transcription factors, kinases, and other regulatory proteins, miRNAs exert tight control over cellular processes and maintain homeostasis. Given the essential requirement for precise cellular coordination in reproductive biology, miRNAs have emerged as key regulators of reproductive function. They participate in multiple stages of reproductive processes, ranging from ovarian function to the establishment and maintenance of pregnancy, thereby influencing fertility outcomes across species. In this review, we summarize recent advances in understanding the roles of miRNAs in key reproductive events, including gametogenesis, oocyte maturation, embryonic genome activation, early embryonic development, implantation and pregnancy. We aim to highlight the principal miRNAs involved in the maintenance of reproductive function and fertility, and their molecular targets and the regulatory networks when known. Based on our review, we conclude that although their potential in clinical and/or agricultural applications still remains uncertain, their role in regulating fundamental aspects of cellular biology, particularly reproductive processes, is becoming increasingly clear.
This study evaluates ChromaLIVETM, a multichromatic, mix-and-read fluorescent marker developed for continuous live-cell imaging, in the context of embryology. The aim was to evaluate whether this marker is compatible with dynamic embryonic development up to the blastocyst stage, with minimal impact on embryo viability, integrity, or normal growth of mouse embryos at the 2-cell stage that were cultured to the blastocyst stage under time-lapse imaging conditions, either in the presence or absence of ChromaLIVETM. Results showed comparable blastocyst formation rates between ChromaLiveTM and the control group, as well as similar proportions of high-quality blastocysts. Although minor but statistically significant delays were noted in two kinetics events (t3 and tSB), other developmental timings remained unaffected. Time-lapse confocal fluorescence imaging demonstrated that ChromaLIVETM dye provided stable, bright, high-resolution 3D visualizations of cellular compartments including membranes, cytoplasm and embryonic structures such as trophectoderm, inner cell mass and blastocoel throughout development. Finally, transcriptomic analyses revealed a limited set of gene-expression differences between stained and unstained embryos; although these included developmental and metabolic pathways, embryos developed to the blastocyst stage comparably to controls.
Connecting the intestinal vasculature with the pre-existing systemic circulatory system is vital for nutrient absorption and blood transport for detoxification in the liver. However, the cellular processes underlying this connection remain unclear. Using genetically modified zebrafish models and in vivo imaging, we visualized that the supra-intestinal artery (SIA) connected to the pre-existing dorsal aorta (DA) in two distinct regions, the anterior and posterior. We found that endothelial cells migrated out of the DA and formed the anterior SIA-DA junction, whereas endothelial cells sprouted from SIA and connected to the DA in the posterior region. Pharmacological and genetic analyses revealed that activin receptor-like kinase 1 (ALK1) signaling was required for the SIA-DA connections. The present study provides new insights into the cellular phenomena and regulatory mechanisms of intestinal vascular development.
