Medical Bulletin 24/February/2024

Here are the top medical news highlights for the day:

New zinc discovery offers promise for cystic fibrosis patients

Researchers from the University of Queensland havediscovered a fault in the bacteria-killing function of immune cells in people with Cystic Fibrosis and a way to reduce infections in people living with it.

Cystic Fibrosis is a chronic disease in which defects in the CFTR (cystic fibrosis transmembrane conductance regulator) channel cause a build-up of mucus in the lungs, airways and digestive system, leading to recurring infections. In people with Cystic Fibrosis, immune cells called macrophages are defective in a zinc pathway that the body uses to kill bacteria.

“One way that macrophages destroy bacteria is by poisoning them with toxic levels of metals such as zinc,” said Professor Matt Sweet,Molecular Bioscience Professor at UQ. “We discovered that the CFTR ion channel is crucial to the zinc pathway and because it doesn’t work properly in people with CF, it may partly explain why they’re more susceptible to bacterial infections.”

Around 70,000 to 100,000 people worldwide are affected by cystic fibrosis, which can reduce life expectancy to an average of 47 years.

The researchers have now identified a zinc transport protein that can restore the macrophages’ ability to kill bacteria when the CFTR protein is not working.

Professor Peter Sly at UQ’s Child Health Research Centre, a paediatric respiratory physician and key collaborator on the project, suggested discovering more about how CF affects the immune system is key to patient care.

“People with CF have a hyper inflammatory state in their airways and are very susceptible to bacterial infections but frequent treatment with antibiotics can often lead to antibiotic-resistant infections,” Professor Sly said.“Current treatments can restore many aspects of CFTR function but they don’t resolve or prevent lung infections so there is a need to restore immune functions.”

“Our goal now is to deliver this zinc transport protein to macrophages in people with CF with the expectation that it would reactivate their immune response and reduce infections,” concluded Professor Sweet.

Reference: DOI: 10.1073/pnas.2315190121

New discovery links gene to incurable birth defect

Researchers from Melbourne-based medical research institute, WEHI, have discovered mutations in a gene can lead to an incurable neurodevelopmental disorder that causes abnormal brain development in newborns and infants.

The study published in Journal eLife reveals that a protein called Trabid helps control neuronal development, and that mutations to this protein can lead to microcephaly – a condition where a baby’s brain is smaller than expected.

Neurons are the fundamental building blocks of the nervous system, responsible for transmitting electrical and chemical signals that enable communication between different parts of the body and the brain.Microcephaly is a neurodevelopmental condition leading to an underdeveloped brain that adversely affects learning and behaviour

“Our understanding into how neurodevelopmental conditions, like microcephaly, develop continues to grow,” Assoc Prof Dewson, a Laboratory Head at WEHI, said. “While previous research has indicated there could be a link between defects in Trabid and microcephaly, our study is the first to provide evidence for the gene’s function in neuronal guidance –filling a vital knowledge gap.”

In 2015, UK researchers published a study that first suggested a possible connection between the gene encoding Trabid (ZRANB1) and microcephaly, after identifying two patients with the brain disorder who had mutations in this gene.

The researchers now suggest that the defects in Trabid, or the proteins that Trabid controls, could help identify babies who are at-risk of developing microcephaly – allowing for potential early interventions.

“Abnormalities in neuron migration and guidance can lead to neurodevelopmental disorders like microcephaly” said Dr HoanhTran.“Cells in the developing brain must migrate to the right location. If the address is missed, developmental defects can occur.Healthy neurons extend long processes called axons in a directional, ordered manner. In our study, we found the neurons from models with defective Trabid project axons that migrate with a wayward trajectory.These significant findings provide an understanding of Trabid/ZRANB1 as a new human microcephaly gene.”

References: DOI: 10.7554/eLife.90796.3

Study suggests excess vitamin B3 could increase heart disease risk

The team, led by Stanley Hazen, M.D., Ph.D., from Cleveland Clinic have discovered a link between 4PY, a breakdown product from excess niacin, and heart disease.

The study, published in Nature Medicine, details genetic links between 4PY and vascular inflammation. The findings provide a foundation for potential new interventions and therapeutics to reduce or prevent that inflammation.

Niacin, also known as vitamin B-3, is one of the eight B vitamins essential for converting food into energy and maintaining healthy skin and nervous system function. Since the body cannot produce niacin on its own, it must be obtained from dietary sources or supplements. Tryptophan, found in animal products, is converted into niacin by the body. Any excess niacin not utilized by the body is eliminated through urine, as it is not stored.

Excessive niacin can lead to an increase in certain blood fats, which may contribute to heart disease risk. Additionally, high doses of niacin can cause flushing, which may worsen existing cardiovascular conditions.

For the study, Dr. Hazen and his team studied the fasting plasma from about 1,100 people with stable cardiac health. Upon analysis, researchers discovered that higher circulating levels of N1-methyl-4-pyridone-3-carboxamide, or 4PY, were strongly associated with the development of a heart attack, stroke, or other unhealthy cardiac events.

The findingssuggested that 4PY directly triggers vascular inflammation which damages blood vessels and can lead to atherosclerosis over time.

“The compound 4PY was identified that is linked to future CVD events” said Dr. Hazen. “We then performed preclinical studies (animal model) and cell-based studies — all of which showed this compound contributes to vascular inflammation. 4PY, it turns out, is a breakdown product made from excess niacin.”

“Our studies found high levels of 4PY in the blood predict future cardiac disease. These new studies help identify a new pathway that contributes to heart disease,” concludedDr. Hazen.

Reference: Cleveland Clinic