Stem Cell Models for Barth Syndrome | Dr. Hilary Vernon - Maryland Stem Cell Research Fund

Barth Syndrome, a rare disease, is an x-chromosome-linked mitochondrial disorder that leads to cardiomyopathy (heart disease) and immunocompromise in patients. The buildup of abnormal cardiolipin, a phospholipid in mitochondrial membranes, is the defect that causes Barth Syndrome. In the Vernon lab, Dr. Hilary Vernon and her team use stem cell models and metabolic analysis to tease apart why Barth syndrome affects certain cell types (e.g. heart muscle) differently than others (e.g. neurons).

-----

Barth Syndrome is a rare disease that affects young males. Barth syndrome presents as heart disease, weakened musculature, and neutropenia (a condition where patients are less able to fight off infection). While advancements have allowed those affected to see past infancy, the disease still strongly impacts patients throughout their life. This disease is caused by mutations in the gene tafazzin, or TAZ. This genetic defect causes a buildup of an abnormal form of the phospholipid cardiolipin. Cardiolipin is one of the major phospholipids of mitochondrial membrane and though nearly all cells have mitochondria in the human body, this disease appears to predominantly affect certain cells, particularly cardiomyocytes (heart muscle cells).

Researchers studying Barth Syndrome have been unable to create a stable knockout mouse line, likely due to the severity of loss of TAZ on viability. Efforts to study Barth Syndrome typically rely on inducible knockdowns of TAZ. These knockdown mice have cardiac impairments, altered cardiolipin profiles, and musculoskeletal deficiencies, similar to Barth Syndrome. However, there is still a need to learn about why heart and muscle cells are more impaired than other cell types and a human model of the disease would increase the likelihood of readily applying discoveries to treatment.

In order to address why some cell types are more affected, Dr. Hilary Vernon and her lab at Johns Hopkins School of Medicine are using stem cell models to determine the mechanistic underpinnings of Barth Syndrome, particularly mitochondrial dysfunction leads to cellular defects. To accomplish their goal, the Vernon lab is generating induced pluripotent stem cells (iPSCs) from Barth Syndrome patients. Creating iPSC cell lines from patients would generate a renewable and relevant source for studying TAZ deficiencies. By differentiating these iPSCs into affected (e.g. cardiomyocytes) or non-affected cell types (e.g. neurons), the Vernon lab hopes to identify the affected metabolic pathways.

Using this information, the Vernon lab hopes to identify a metabolite or pathway that can be used as a therapeutic target, potentially through dietary supplements or medications. Since Barth Syndrome patients have very poor prognosis, a treatment that can rectify the impacted metabolic pathways would greatly improve the quality of life for individuals suffering from this disease.

Dr. Vernon credits the Maryland Stem Cell Research Fund (MSCRF) for the support which allowed her lab to generate the foundational stem cell model that is pivotal to her research. Dr. Vernon is also a physician at the Kennedy Krieger Institute and specializes in other mitochondrial diseases. Support from the MSCRF facilitates a balance between her research and her ability to help patients directly, allowing her to have both immediate and long-term impacts on those impacted by Barth Syndrome.

------------
Interested in having your research funded by the Maryland Stem Cell Research Fund?

Or, follow us on LinkedIn or Twitter to learn about opportunities: