Image: (A) Healthy Cells with normal mitochondria. (B) BTHS cells with elongated and abnormal mitochondria. Image copyright by International Journal of Molecular Sciences, PMID 31336787
Promising results were recently published demonstrating gene replacement can lead to improved mitochondrial structure and function, signaling the possibility to reverse the underlying biology of Barth syndrome. Using cells obtained from individuals with different TAZ mutations of varied severity in Barth syndrome, Suzuki-Hatano et al. tested the impact of AAV-TAZ transduction in a cellular model and found that providing a functional copy of tafazzin improves mitochondrial processes in cells affected by Barth syndrome.
Alongside previously studies analyzing human proteins and the impact of AAV-TAZ transduction in a Barth syndrome (knockdown) mouse model, the collaborative research team at the University of Florida and Washington University continue to generate a body of work that will support an investigational new drug (IND) application to FDA and pave a path towards the clinical translation of gene replacement therapy in Barth syndrome.
This important research was funded in part by Barth Syndrome Foundation's Research Grant program.
On September 6th, BSF participated in the U.S. Food and Drug Administration (FDA) stakeholder workshop to address recent advancements and key challenges facing mitochondrial diseases.
Given the complexities of mitochondrial diseases and, by extension, the challenges of designing informative clinical trials in this group of rare diseases, this scientific symposium brought together academic physicians, FDA regulatory experts, and experts from related disciplines to exchange ideas on ways to address the challenges and to promote drug development in this challenging field. The timely agenda included presentations on the state of the basic science and clinical study approaches by Dr. Robert Naviaux (UCSD) and Dr. Amel Karaa (MGH) respectively; lessons learned and key findings from current and completed trials discussed by Matt Klein (BioElectron), Jim Carr (Stealth Biotherapeutics), and BSF's own Scientific and Medical Advisory Board member, Michio Hirano (Columbia University).
BSF’s Executive Director, Emily Milligan, rounded out the patient advocacy perspective of the discussions alongside Mindy Leffler (Casimir Trials) and Phil Yeske (UMDF). BSF’s central takeaway from the discussion is the importance of understanding the natural history of BTHS, which we continue to address by supporting the Barth Syndrome Patient Registry, on-site research conducted during the International BSF conference, and Barth syndrome clinics led by Hilary Vernon (JHMI), Germaine Pierre and Effie Chronopoulou (NHS, Bristol UK).
BSF hosted an Externally-Led Patient-Focused Drug Development (PFDD)
meeting in 2018 to share with officials at FDA and other stakeholders
(e.g., industry and research institutions) the perspectives of people
living with Barth syndrome (BTHS), its impact on their daily lives, and
their expectations and priorities for current and future treatments for
This month, the FDA published Barth Syndrome Foundation's Voice of the Patient Report
on its website as a resource for organizations to identify and
organize opportunities to generate public collaborations such as the PFDD meeting. This milestone continues to provide BSF the
platform to engage with drug developers and regulatory representatives
by sharing firsthand experience of what it means to have Barth syndrome.
Notably, BSF had one of the highest attendance rates of any externally-led PFDD meeting, with more than 25% of the world’s known BTHS-affected population represented. The subsequent "Voice of the Patient: Barth Syndrome" report is a compilation of the testimonies and survey responses of individuals affected by Barth syndrome from all around the world and is the first-ever report of its kind for this ultra-rare condition.
Your ideas, comments and suggestions are welcome! Submit your feedback directly via email: Erik.Lontok@barthsyndrome.org
BSF 2019 Call for Proposals, Application Due Date - 10/31/19