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Research & Development Grants

Research & Development Grants


The BSF research and development grants support advancing treatments for Barth syndrome while fostering collaborative research as we work to achieve our vision of a world in which Barth syndrome no longer causes suffering or loss of life.

 

 


2021 GRANT AWARDS


 

Vetted by BSF’s Scientific and Medical Advisory Board (SMAB), 2021 grantees’ projects span novel areas of Barth basic science, drug repurposing and testing in the heart-specific TAFAZZIN knockout mouse, and remotely conducted clinical research.

 

Activating Pyruvate Dehydrogenase Complex to Improve Barth Syndrome Cardiac Function

Charles E. McCall, PhD, Professor, Wake Forest University Health Sciences

Development Award, $100,000 over two years

 

Awarded to the multi-disciplinary team of Professors Charles McCall, Miriam Greenberg, Peter Stacpoole, and Boone Prentice, this Development Award will investigate the drug dichloroacetate‘s (DCA) impact on the heart-specific TAFAZZIN knockout mouse. Involving animal research at Wake Forest University (McCall), cellular and cardiolipin expertise from Wayne State University (Greenberg), and clinical experience and research tools via the University of Florida (Stacpoole & Prentice), this mouse project asks whether DCA can be repurposed as an investigational drug and potential therapy for Barth syndrome.

This project’s funding was made possible by the generous support of the Will McCurdy Fund for Advancement in Therapies for Barth Syndrome.

 

Cardiolipin synthesis and remodeling regulate mitochondrial metabolic plasticity and signaling function

Mauro Corrado, PhD, University of Cologne

Idea Award, $50,000 over one year

 

Awarded to Dr. Mauro Corrado, this Idea Award builds upon novel findings that cardiolipin plays a key role in the development and function of T cells - immune cells that play a role in adaptive immunity. Utilizing mouse models, Dr. Corrado is focusing on the implications of impaired immune function and its impact on the health and function of mouse muscle cells. Given the immune issues faced by affected individuals, this effort has the potential to provide a more holistic view of immune dysfunction in Barth syndrome.

This project’s funding was made possible by the generous support of the Paula and Woody Varner Fund.

 

Surveying TAZ genetic interactions and mutational landscape in human cells

Jason Moffat, PhD, Professor, University of Toronto

Idea Award, $50,000 over one year

 

Awarded to Prof. Jason Moffat and Prof. Charles Boone of the University of Toronto, this Idea Award enables us to better understand the TAFAZZIN gene, in and out. Inwardly, Dr. Moffat proposes to connect changes in gene sequences to their functional consequences on protein function. Known as deep mutational scanning, this effort has the potential to expand our understanding about gene variants in our community. Outwardly, via a CRISPR-mediated genome-wide screen, Dr. Moffat proposes to identify genes that interact with TAFAZZIN and recorded gene variants. By increasing our understanding of TAFAZZIN interactions as well as gene variants and mutations’ impact on tafazzin protein function, the research team seeks to identify insights into the variable manifestations, or phenotype, of Barth syndrome.

This project’s funding was made possible by generous contributions from our affiliates Barth Syndrome Foundation of Canada and the Barth Syndrome UK.

 

“What is Barth Tired?”: A mixed methods approach to qualifying and quantifying fatigue in males with Barth syndrome

Stacey E. Reynolds, PhD, Assistant Professor, Virginia Commonwealth University

Idea Award, $50,000 over one year

Awarded to Associate Prof. Stacey Reynolds and in collaboration with Assistant Prof. Virginia W. Chu of Virginia Commonwealth University, this Idea Award aims to capture the fatigue experienced and voiced by our affected individuals.  Dr. Reynolds’s team will first conduct interviews with affected individuals, siblings, and parents to capture the impact of fatigue on daily living. Dr. Chu will then capture individuals’ self-assessment of fatigue in real-time using a novel phone application and map those ratings onto activity data collected by wrist-worn watches worn by affected individuals. This mixed-methods approach aims to qualify and quantify fatigue in our community and is in direct response to the narratives shared during BSF’s 2018 Patient Focused Drug Development meeting with the U.S. FDA.

This project’s funding was made possible by the generous support of the Will McCurdy Fund for Advancement in Therapies for Barth Syndrome.


ONGOING GRANT PROJECTS


 

Development of mitochondria-targeted peptide compounds as Barth syndrome therapeutics

Nathan Alder, PhD, Associate Professor, University of Connecticut, Storrs, CT

Award - $50,000 over 1-year period

Awarded to Associate Professor Nathan Alder of University of Connecticut, this project will first ask how Szeto-Schiller compounds impact mitochondrial function – of which elamipretide is a member. These findings will then allow Dr. Alder and his team to focus on developing Szeto-Schiller compounds tailored to treat Barth syndrome. The potential impact of this project stems from Dr. Alder’s ideal expertise in cell-free model systems, alongside our increasing knowledge of the safety and efficacy (or positive impact) of elamipretide in our affected individuals. This project’s funding was made possible by the generous support of the Will McCurdy Fund for Advancement in Therapies for Barth Syndrome.

 

Deuterated polyunsaturated fatty acids as protective therapy in the treatment of Barth syndrome

Catherine F. Clarke, PhD, Professor and Chair, University of California at Los Angeles, Los Angeles, CA (UCLA)

Award—US $100,000 over 2-year period

Barth syndrome is uniquely associated with a deficiency and alterations in cardiolipin, a phospholipid that is an important component of the inner mitochondrial membrane. This deficiency and alterations in cardiolipin result in damage to the cell. Providing a “disease-resistant” cardiolipin to increase and replace the usual molecules may be therapeutic for individuals with Barth syndrome.

To test this hypothesis, Dr. Catherine Clarke of UCLA will apply this unique therapeutic idea by using chemically modified lipids to reduce the amount of cellular damage produced by deficient and altered cardiolipin.

If this novel specific lipid-replacement therapy preserves mitochondrial function, it could protect cells against the oxidative stress conditions known to exist in people with Barth syndrome.

This grant is made possible by support from the Will McCurdy Fund for Advancement in Therapies for Barth Syndrome

 

Investigation of a new nutraceutical for treatment of Barth Syndrome

Robin E. Duncan, PhD, Associate Professor, University of Waterloo, Waterloo, ON, Canada

2020 Award - $41,580 over 2-year period 

Awarded to Associate Professor Robin Duncan of University of Waterloo, this project will assess the therapeutic potential and activity of a nutraceutical (a possible supplement therapy that is available without prescription) in preserving the viability of Barth syndrome cells. Following up on early results that this nutraceutical has the ability to help Barth syndrome cells survive at the same levels as normal cells, Dr. Duncan and her team will try to understand what is the process that helps preserve these cells, and further expand her research into the Taz knockout (TAZKO) mouse model. As an early stage research effort (aka preclinical study), this research aims to provide the foundational understanding of this nutraceutical and its impact on Barth syndrome. This project’s funding was made possible by generous contributions from our affiliates Barth Syndrome Foundation of Canada and the Barth Syndrome UK.

 

Structural and Biophysical Studies of Tafazzin

Steven Glynn, Associate Professor, Stony Brook University, Stony Brook, NY

2020 Award - $50,000 over 2-year period

 

Awarded to Associate Professor Steven Glynn of Stony Brook University, whom is a trained crystallographer (someone who purifies and generates protein crystals for structural studies). Dr. Glynn will apply his experience towards purifying normal and variant versions of Taz from yeast. If successful, he will determine what normal Taz looks like and how variant versions look and function differently. This important discovery science project will shed light on how some of the TAZ variants we know of and track impact Taz activity. As every biochemistry student learns early on – protein structure dictates function. This project’s funding was made possible by a generous contribution from our affiliate Association Syndrome de Barth France.

 

Cardiolipin Requirement for Mitochondrial Calcium Import

Vishal Gohil, PhD, Associate Professor, Texas A&M University, College Station, TX

Award - $50,000 over 1-year period

Awarded to Associate Professor Vishal Gohil of Texas A&M University, this discovery science project aims to understand how levels of calcium, mature cardiolipin (CL), and energy generation play a role in Barth syndrome. By using the highly modifiable yeast system, Dr. Gohil will probe what happens with reduced levels of mature CL (which is what happens in Barth syndrome) and its subsequent impact on the amount of calcium inside and outside of the mitochondria. Studying this relationship may further shed light on why Barth syndrome mitochondria produce lower levels of energy.

 

Resolution of the underlying basis for the impaired oxidation of fatty acids in Barth syndrome

Riekelt Houtkooper, PhD, Professor, Amsterdam Medical Center, Amsterdam, The Netherlands

Award—US $50,000 over 1-year period

Barth syndrome is a unique mitochondrial disease. Another type of mitochondrial disease that has common attributes with Barth syndrome is fatty acid oxidation (FAO) disorders. This is a group of diseases that affect approximately 1 in 10,000 births making it 30 times more numerous than Barth syndrome. 

Dr. Riekelt Houtkooper of Amsterdam Medical Center will investigate how closely Barth syndrome resembles fatty acid oxidation disorders. Dr. Jan Dudek of University Medical Center Würzburg will collaborate with Dr. Houtkooper’s group to study the relationship of fatty acid oxidation and heart failure as it relates to Barth syndrome.  

These projects aim to explain why underlying defective mechanisms in Barth syndrome impair the body’s ability to use fatty acids properly. Similarly, researchers aim to resolve the cause for the diminished oxidation of fatty acids in Barth syndrome with the ultimate goal of informing novel therapeutic strategies.

This grant is made possible in part by support from Association Syndrome de Barth France

 

Prenatal cardiac phenotype as a platform for testing Barth syndrome therapies

Colin Phoon, MPhil, MD, Associate Professor, New York University School of Medicine, New York, NY

Award: US $70,000 over 2-year period

Partial funding for this award was provided by the Paula and Woody Varner Fund

 

Essential activities of Tafazzin that are independent of cardiolipin remodeling

William T. Pu, MD, Professor, Boston Children's Hospital, Boston, MA

Award - $50,000 over 1-year period

Awarded to Professor William Pu of Boston Children’s Hospital and a member of the BSF SMAB, this project aims to understand the functions of mouse tafazzin (Taz) beyond generating mature cardiolipin (CL). By utilizing the Taz knockout (TAZKO) mouse model, Dr. Pu and his team found that replacing the Taz gene with different versions (variants of Taz), resulted in different levels of rescue for the TAZKO mice. Using these variant Taz versions as bait for proteins that interact with Taz, Dr. Pu and his research team hope to identify what are the other proteins that work with Taz independent of its CL-modifying function. 

 


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