(Press-News.org) In a Nature Metabolism paper published today, researchers from the University of Pittsburgh detail a potential new target and a small-molecule drug candidate for treating Barth syndrome, a rare, life-threatening and currently incurable genetic disease with devastating consequences.
Barth syndrome affects about 1 in every 300,000 to 400,000 babies born worldwide. Those with the condition have weak muscles and hearts and experience debilitating fatigue and recurrent infections.
Pitt researchers discovered that faulty mitochondria are at least partially to blame, and identified a molecular culprit that could be targeted to potentially reverse the disease course in the future.
In healthy people, a lipid known as cardiolipin, or CL, undergoes a series of transformations, known as remodeling, within the mitochondria, explains senior author of the study Dr. Valerian Kagan, professor of environmental and occupational health at the University of Pittsburgh School of Public Health.
In people with Barth syndrome, however, a crucial mitochondria-housed gene, called tafazzin (TAZ), is mutated. Without TAZ, CL remodeling is stopped in its tracks and harmful lipids accumulate.
For this latest investigation, the team used computational models as well as in-vitro studies in both mouse myoblast cells and human heart-tissue samples from people with Barth syndrome.
“We found that lyso-cardiolipin, an intermediate accumulating in mutant TAZ-deficient cells, interacts with the mitochondrial protein cytochrome c, converting it to a demon enzyme that oxidizes everything around it,” said Kagan.
As it turns out, this excessive oxidation in TAZ-deficient cells could be prevented. The team showed that a compound known as imidazole-substituted oleic acid, or IOA, could block the formation of those complexes and improve the motor function and endurance in a fruit fly model of Barth syndrome.
In the future, this discovery could pave way for correcting genetic tafazzin deficiency and improving mitochondrial function through small-molecule therapeutics.
Journalists interested in learning more can contact mediarelations@upmc.edu.
END
Potential new target and drug candidate for Barth syndrome
2023-11-23
ELSE PRESS RELEASES FROM THIS DATE:
New therapy can treat rare and hereditary diseases
2023-11-23
A lot of research has been done over many decades on diseases that are widespread in large parts of the population, such as cancer and heart disease. As a result, treatment methods have improved enormously thanks to long-term research efforts on diseases that affect many people.
However, there are many diseases that affect just a handful people. These diseases often fly under the radar and are far less researched. They include quite a few rare, hereditary diseases, such as DOOR syndrome, which is ...
Y-chromosome and its impact on digestive diseases
2023-11-23
A major breakthrough in human genetics has been achieved with the complete decoding of the human Y chromosome, opening up new avenues for research into digestive diseases. This milestone, along with advancements in third-generation sequencing technologies, is poised to revolutionize our understanding of the genetic underpinnings of digestive disorders and pave the way for more personalized and effective treatment strategies.
The Y chromosome, the smallest of the human chromosomes, has long been shrouded in mystery due to its complex repetitive structure. However, recent advancements in sequencing technologies have enabled researchers to unravel the intricate details of this genetic ...
Fractional COVID-19 booster vaccines produce similar immune response as full-doses
2023-11-23
Reducing the dose of a widely used COVID-19 booster vaccine produces a similar immune response in adults to a full-dose with fewer side effects, according to a new study.
The research, led by Murdoch Children's Research Institute (MCRI) and the National Centre for Communicable Diseases in Mongolia, found that a half dose of a Pfizer COVID-19 booster vaccine elicited a non-inferior immune response to a full dose in Mongolian adults who previously had AstraZeneca or Sinopharm COVID-19 shots. But it found half-dose boosting may be less effective in adults primed with the Sputnik V COVID-19 vaccine.
The research ...
Consolidator Grants: ERC unleashes €627 million in grants to fuel excellent research across Europe
2023-11-23
Iliana Ivanova, European Commissioner for Innovation, Research, Culture, Education and Youth, said: “I extend my heartfelt congratulations to all the brilliant researchers who have been selected for ERC Consolidator Grants. I'm especially thrilled to note the significant increase in the representation of women among the winners for the third consecutive year in this prestigious grant competition. This positive trend not only reflects the outstanding contributions of women researchers but also highlights the strides we are making towards a more inclusive and diverse scientific community.”
President of the European Research Council Prof. Maria Leptin said: “The new ...
A fifth higher: Tropical cyclones substantially raise the Social Cost of Carbon
2023-11-23
Extreme events like tropical cyclones have immediate impacts, but also long-term implications for societies. A new study published in the journal Nature Communications now finds: Accounting for the long-term impacts of these storms raises the global Social Cost of Carbon by more than 20 percent, compared to the estimates currently used for policy evaluations. This increase is mainly driven by the projected rise of tropical-cyclone damages to the major economies of India, USA, China, Taiwan, and Japan under global warming.
“Intense tropical cyclones have the power to slow down the economic development of a country for more than a decade, our analysis shows. With global warming, the share ...
Study reveals how shipwrecks are providing a refuge for marine life
2023-11-23
An estimated 50,000 shipwrecks can be found around the UK’s coastline and have been acting as a hidden refuge for fish, corals and other marine species in areas still open to destructive bottom towed fishing, a new study has shown.
Many of these wrecks have been lying on the seabed for well over a century, and have served as a deterrent to fishers who use bottom towed trawling to secure their catches.
As a result, while many areas of the seabed have been damaged significantly in areas of heavy fishing pressure, the ...
Pangenomic study of water caltrop — structural variations play a role in speciation and asymmetric subgenome evolution
2023-11-23
Rice, maize, and wheat provide more than half of the calories consumed by humans. The decrease in crop diversity poses a significant risk to global food security. Therefore, the utilization of orphan crops has become an effective approach to address food security crises. Nevertheless, in the face of rapid urban and rural modernization and the intensification of agricultural practices, the availability of wild and cultivated orphan crops is dwindling, with a noticeable disparity in their collection, preservation, ...
Professor Tao Jun's team at Yangzhou University analyses the molecular mechanism of PoWRKY71 in response to drought stress of Paeonia ostii
2023-11-23
Paeonia ostii is a widely grown woody crop with up to 40% α-linolenic acid in its seed oil, which is beneficial to human health. Drought is a major environmental factor limiting the popularisation of P. ostii in hilly and mountainous areas, which may affect plant growth or lead to plant death.WRKY is one of the largest families of transcription factors in plants, and plays an important role in plant response to drought stress. However, the molecular mechanism by which P. ostii WRKY transcription factors respond to drought stress is still unclear.
In September 2023, Horticulture ...
The Chinese team completed the genome assembly of Cornus wilsoniana
2023-11-23
Cornus wilsoniana (2n=22) is a common shrub in the northern temperate zone of China. It blooms white flowers in spring and produces purple-black berries in autumn. This tree has a unique mottled bark texture that makes it particularly eye-catching in winter, earning it the common name "ghost dogwood". Due to its peeling bark in winter, it is commonly known as "Guangpi tree" in China. The fruit of C. wilsoniana is rich in oil and can be used to extract edible oil. The oil content ...
Does patient-surgeon gender concordance lead to lower patient mortality? Mostly no, UCLA-led research suggests
2023-11-23
Does patient-surgeon gender concordance lead to lower patient mortality? Mostly no, UCLA-led research suggests
New research finds little evidence that post-surgical patient mortality is lower when patient and surgeon are the same gender.
While gender concordance has been shown to improve patient care in other health specialties, evidence has been limited when it comes to concordance between patient and surgeon. This study shows that gender concordance was associated with lower mortality for female patients, but higher mortality for male patients—patient mortality was the lowest for ...