The new study entitled, "Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome", was recently published in the Proceedings of the 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.
Link to full article published in Proceedings of the National Academy of Sciences: http://www.pnas.org/content/106/7/2337.full?sid=14754cf1-3343-490f-a418-ef589e10e510
Lauren Woods | EurekAlert!
Further reports about: > BTHS > Barth syndrome > Drosophila > NYU > Proceedings of the National Academy of Sciences > Science TV > Syndrome > X-linked genetic cardioskeletal muscle disease > bacterial infection > blood cell > calcium-independent phospholipase A2 > cardiolipin pathway > cell biology > genetic disorder > iPLA2-VIA inhibitor > muscle weakness > pathogenesis > white blood cell
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses