Elevated hormone flags liver problems in mice with methylmalonic acidemia. Researchers have discovered that a hormone, fibroblast growth factor 21 (FGF21), is extremely elevated in mice with liver disease that mimics the same condition in patients with methylmalonic acidemia (MMA), a serious genomic disorder. Based on this finding, medical teams treating patients with MMA will be able to measure FGF21 levels to predict how severely patients’ livers are affected and when to refer patients for liver transplants.

The findings also might shed light on more common disorders such as fatty liver disease, obesity and diabetes by uncovering similarities in how MMA and these disorders affect energy metabolism and, more specifically, the function of mitochondria, the cells’ energy powerhouses. The study was conducted by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health.

“Findings from mouse studies usually take years to translate into health care treatment, but not in this case,” said Charles P. Venditti, M.D., Ph.D., senior author and senior investigator in the NHGRI Medical Genomics and Metabolic Genetics Branch. “We can use this information today to ensure that patients with MMA are treated before they develop severe complications.”

MMA is a genomic disease that impairs a person’s ability to break down food proteins and certain fatty acids. The condition affects roughly 1 in 50,000 children born in the United States and can be detected through newborn screening. Children with MMA suffer from frequent life-threatening metabolic crises when they encounter a minor viral illness or other stressors like trauma, dietary imbalance or surgery. They must adhere to a special low-protein diet and take various supplements their entire lives.

The NHGRI team created a new mouse model and used it to discover key pathways that were affected during a fasting challenge to model a metabolic crisis in a patient with MMA. It enabled them to identify markers that they could then measure in MMA patients to assess the severity of the dysfunction in their mitochondria, specifically in the liver.
The MMA mice also allowed them to study the response to liver-directed gene therapy and to compare the findings in patients after liver transplant surgery. Liver transplants give patients with MMA a missing enzyme and ease some of the symptoms, but do not cure the disease. Kidney transplantation, on the other hand, is necessary when these patients reach terminal stages of renal failure, an expected chronic complication of MMA. Selecting which patients would benefit from a liver or combined liver/kidney transplant as opposed to just a kidney transplant is an important clinical decision for families and their clinicians.

“We found that having MMA, whether in a mouse or person, causes stress pathways to be chronically activated and can impair their ability to respond to acute stress,” said Irini Manoli, M.D., Ph.D., lead author and associate investigator in NHGRI’s Medical Genomics and Metabolic Genetics Branch. “Our new markers can accurately predict how effective a therapy, whether cellular or genomic, might be for the patients.”
National Human Genome Research Institutewww.genome.gov/news/news-release/Elevated-hormone-flags-liver-problems-in-mice-with-methylmalonic-acidemia-MMA

In healthy individuals, the Zika virus causes flu-like symptoms. If a pregnant woman becomes infected, the unborn child can suffer from severe brain abnormalities as a result of mechanisms that have not yet been explained. A study by the Technical University of Munich (TUM) and the Max Planck Institute of Biochemistry (MPI-B) shows that Zika virus proteins bind to cellular proteins that are required for neural development.

A few years ago, Zika virus spread across South America, posing a health issue with global impact. A significant number of South American women who came into contact with the virus for the first time at the start of their pregnancy by a mosquito bite subsequently gave birth to children with severe disabilities. The babies suffered from a condition known as microcephaly; they were born with a brain that was too small. This can lead to intellectual disabilities and other serious neurological disorders.

Scientists succeeded in proving that these deformities are caused by Zika virus infections, but so far they have been unable to explain why. Andreas Pichlmair, Chair for Viral Immunopathology at TUM and his team from the TUM Institute of Virology and MPI-B have examined how Zika virus influences human brain cells. They identified the virus proteins with the potential to affect neuronal development in the developing brain.

 “Zika virus is closely related to the Hepatitis C virus and certain tropical diseases such as Dengue and West Nile virus. It is, however, the only virus that causes brain damage in newborns,” explains Pichlmair, who headed the recent study.

The researchers discovered that the virus uses certain cellular proteins to replicate its own genome. These molecules are also important neurological factors in the process of a stem cell developing into a nerve cell. “Our findings suggest that the virus takes these factors away from brain development and uses them to replicate its genome, which prevents the brain from developing properly,” explains the virologist.

When the team headed by Pichlmair removed the factors in the cells, the virus found it much harder to replicate. The researchers were able to demonstrate which virus proteins come in contact with these development factors and cause the brain defects. “Previous studies revealed the virus proteins necessary for the packaging or replication of the viral genome but it was enigmatic to understand how these proteins influence neuronal development. It appears that viral proteins are responsible for causing the serious defects in the unborn – unintentionally we presume,” says Pichlmair.

In their comprehensive proteomics survey, the research team identified cellular proteins that were altered chemically or numerically by the virus or which bound to virus proteins. In this way, they were not only able to illustrate possible reasons for the caused deformities, but also obtained a very clear picture of how the virus reprograms the cell to use it for its own replication. www.tum.de/nc/en/about-tum/news/press-releases/details/34920/

The battle against cancer hinges on the early detection and then delivery of effective treatment. Oncimmune is working to revolutionise both the detection of cancer and its treatment by harnessing the sophisticated disease-detecting capabilities of the immune system to find cancer in its early stages. Oncimmune’s range of diagnostic tests assist clinicians to identify the presence of cancer on average four years before standard clinical diagnosis, whilst its technology platform and sample biobanks are helping healthcare companies to develop new cancer treatments.

Starna, established 1964, has a worldwide reputation for quality, service and innovation in the production and supply of spectrophotometer cells, optical components and Certified Reference Materials (CRMs). World-leader with over 50 years’ experience in the production of Certified Reference Materials for UV-Vis-NIR & Fluorescence spectroscopy; it is the only company to achieve both ISO/IEC 17025 and ISO 17034 for this range of products. A highly regarded manufacturer of high precision quartz and glass Cells/Cuvettes for Photometers and Fluorimeters. Starna sells worldwide to instrument manufacturers, pharmaceuticals, life-biosciences, R&D laboratories, medical companies and universities.