Barth Syndrome
Barth syndrome is an X-linked mitochondrial lipid disorder that results from the mutation of the TAFAZZIN (TAZ) gene which codes for an acyltransferase/transacylase needed for the mitochondrial cardiolipin biosynthetic pathway. One of the most serious signs of Barth syndrome is cardiomyopathy. Protheragen is an innovative research service provider that provides services in drug discovery and development of rare cardiovascular disorders like Barth syndrome. Our goal is to provide one-stop services that streamline the research process for our clients.
Overview of Barth Syndrome
Barth syndrome's estimated frequency is around one case per million births and mostly occurs in men. Males suffering from Barth syndrome typically have cardiomyopathy, skeletal myopathy, and prepubertal growth retardation along with delayed neutropenia, and distinct facial features. Before five years of age, a child is almost always diagnosed with cardiomyopathy which in most cases is dilated cardiomyopathy. He may or may not also have endocardial fibroelastosis or left ventricular noncompaction. In some cases, individuals can also suffer from hypertrophic cardiomyopathy.
Fig.1 Key discoveries in Barth syndrome cardiomyopathy. (Pang, J., et al., 2022)Pathogenesis of Barth Syndrome
Barth syndrome is an uncommon genetic disease with an X-link inheritance pattern. It is the result of mutations in the TAZ gene located at Xq28. Tafazzin participates in the biosynthetic pathway of cardiolipin, a unique phospholipid almost exclusively localized to the mitochondrial membranes. Cardiolipin interacts with several essential protein complexes in the mitochondrial membranes, such as the respiratory chain, mitochondrial metabolite carriers, and proteins that contribute to the remodeling of mitochondria.
Fig.2 Molecular mechanism of Barth syndrome. (Pang, J., et al., 2022)Defective TAZ and abnormal cardiolipin in Barth syndrome cause lesions in the bioenergetics and morphogenesis architectures of the mitochondria, as well as in the homeostasis of reactive oxygen species (ROS) and calcium ions (Ca2+).
Therapeutics Development for Barth Syndrome
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Elamipretide | Binds to cardiolipin on the inner mitochondrial membrane which results in elevated membrane stability, and lowered production of ROS. | Cytochrome c peroxidase | NCT03098797 | Phase II |
| Triheptanoin | By increasing the supply of intermediary compounds of the TCA cycle, triheptanoin contributes to the improvement of overall mitochondrial bioenergetics. | / | NCT01461304 | N/A |
| AAV-Taz gene therapy | Elevate Taz protein levels and remarkably augment cardiac systolic function beyond untreated levels. | Taz | / | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
A wide range of services is available at our company, including diagnostics, therapeutics, and disease model development. Furthermore, our skilled teams conduct pharmacokinetic investigations and preclinical safety evaluations, thus providing holistic support for your research. We equip researchers and pharmaceutical companies with the insight gained from years of attending to the multitude of difficulties associated with rare diseases, allowing us to customize our services as needed.
Therapeutic Development Services
Animal Model Development for Barth Syndrome
Research from animal models greatly contributes to our understanding of TAZ function and Barth syndrome and is irreplaceable in the evaluation of potential therapies for Barth syndrome. We specialize in custom animal model development for purposes related to the study and therapy of Barth syndrome.
Animal models are typically constructed using advanced techniques to create targeted mutations in the TAZ gene in animals, thereby replicating the mitochondrial defects observed in the disease.
Optional models: Taz-KD model, Taz-Flox model, Taz-KO model, Taz-CKO model, etc.
Here at Protheragen, we work tirelessly to expedite the transition from discovery to therapy. Collaborating with us unlocks access to advanced technologies and a team of specialists focused on improving the understanding and therapy of uncommon cardiovascular diseases. If our services interest you, please reach out to us.
Reference
- Pang, Jing et al. "Barth Syndrome Cardiomyopathy: An Update." Genes 13.4 (2022): 656.
For research use only, not for clinical use.