New Potential Therapeutic Target Discovered for Genetic Disorder – Barth Syndrome

	Tweet

Researchers at NYU Langone Medical Center may have discovered a new targeted intervention for Barth Syndrome (BTHS). BTHS, a sometimes fatal disease, is a serious genetic disorder occurring predominantly in males that leads to infection or heart failure in childhood. The new study entitled, “Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome”, was recently published in the Proceedings of National Academy of Sciences, shows the benefits of targeted intervention with an iPLA2-VIA inhibitor that prevents a major symptom of the disease- cardiolipin deficiency.

“Our research has established a causal role of cardiolipin deficiency in the pathogenesis of Barth syndrome and identified an important enzyme in cardiolipin degradation called iPLA2-VIA as a potential target for therapeutic intervention of the disease,” said Mindong Ren, Ph.D., lead investigator of the study and assistant professor of cell biology at NYU Langone Medical Center.

BTHS syndrome is an X-linked genetic cardioskeletal muscle disease resulting in muscle weakness and fatigue in patients. The debilitating disorder is caused by a mutation in the genetic coding of tafazzin, an enzyme of the cardiolipin pathway. Cardiolipin is an essential lipid in the inner membrane of mitochondria responsible for normal cell structure and energy production. BTHS patients exhibit defects in cardiolipin metabolism which help fight infections. The various symptoms of BTHS, in addition to cardiolipin deficiency, include cardiomyopathy (weakness in heart muscle), neutropenia (a reduction in neutrophils or white blood cells that fight bacterial infections), muscle weakness & fatigue (caused by cellular deficiency), growth delay, and increase of organic acids in urine. 

In a previous study, NYU researchers documented the characteristics of a tafazzin-deficiency in a Drosophila (fruit fly) model of the disease, showing low and abnormal cardiolipin concentration, abnormal mitochondria, and poor motor function. In this new study researchers documented that tafazzin or cardiolipin deficiency in Drosophila disrupts the final stage of spermatogenesis causing male sterility. Using this fly model, the study showed that this trait of cardiolipin deficiency can be genetically suppressed by inactivating calcium-independent phospholipase A2, which prevents the degradation of cardiolipin. This method keeps cardiolipin levels normal. Researchers were also able to show that treatment of BTHS patients lymphoblasts within a tissue culture with the iPLA2-VIA inhibitor BEL partially restored the tissue cultures cardiolipin homeostasis.

“Taken together, our two findings establish a causal role of cardiolipin deficiency in the pathogenesis of Barth syndrome and identify iPLA2-VIA as a very important enzyme,” said Michael Schlame, M.D., associate professor of anesthesiology and cell biology, NYU Langone Medical Center. “This is good news for patients since this enzyme is now a potential target for therapeutic intervention.”

According to researchers, although this has not been tested in humans, the successful restoration of these mutated cells with BEL shows promise for continued BTHS research, patients and their families. There are no treatments for Barth syndrome at this time.

This study was funded in part by grants from the Barth Syndrome Foundation, the United Mitochondrial Disease Foundation, and NIH.

About NYU Langone Medical Center
Located in the heart of New York City, NYU Langone Medical Center is a premier center for health care, biomedical research, and medical education. For over 167 years, NYU physicians and researchers have contributed to the practice and science of medicine. Today the Medical Center consists of NYU School of Medicine; Rusk Institute of Rehabilitation Medicine, the first and largest facility of its kind; NYU Hospital for Joint Diseases, a leader in musculoskeletal care; and such nationally recognized programs as the NYU Cancer Institute, the NYU Child Study Center, and the NYU Cardiac and Vascular Institute.

Source: New York University Langone Medical Center

RELATED STORIES:
FDA Allows Qualified Health Claim to Decrease Risk of Coronary Heart Disease   Wrong Dose of Heart Meds Too Frequent in Children   Boston Scientific, J&J stents aid high-risk cases   Bone marrow stem cells generate heart tissue   U of T researchers find link between childhood physical abuse and heart disease   U.S. Panel Recommends Limiting Gene Therapy Trials   Gene migration helps predict movement of disease   Air pollution a serious threat to heart health   Low-Carb Diets Linked to Atherosclerosis and Impaired Blood Vessel Growth   Multislice CT Speeds the Diagnosis of Chest Pain in the Emergency Room   Women with heart disease not taking aspirin   Study Examines Stroke Risk Among Patients Undergoing Cardiac Surgery

Comments

[ + Post Your Own ]

Now you're in the public comment zone. What follows is not Armenian Medical Network's stuff; it comes from other people and we don't vouch for it. A reminder: By using this Web site you agree to accept our Terms of Service. Click here to read the Rules of Engagement.

There are no comments for this entry yet. [ + Comment here + ]