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
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences