The FDA has faced criticism over its handling of the approval process for AstraZeneca’s ticagrelor, a multibillion-dollar medication used to treat acute coronary syndrome. The concerns were raised by an investigation conducted by The BMJ, which found serious issues with key platelet studies that supported the drug’s approval.

For over a decade, ticagrelor has been recommended for patients suffering from sudden reduced blood flow to the heart. However, in December last year, The BMJ uncovered data integrity problems in the landmark clinical trial (PLATO) used to gain worldwide approval for the medication. This led to questions about the drug’s advantage over cheaper rivals.

The latest investigation by The BMJ delves deeper into two crucial platelet studies that AstraZeneca claimed explained ticagrelor’s effectiveness in treating acute coronary syndrome. Unfortunately, it has been discovered that the primary endpoint results for both trials were inaccurately reported in the leading cardiology journal, Circulation.

What’s more, an analysis of data from platelet machines used in these trials revealed that over 60 out of 282 readings were missing from FDA datasets. This raises serious concerns about the reliability and accuracy of the research conducted on ticagrelor.

Victor Serebruany, an adjunct faculty member at Johns Hopkins University and a prominent critic of ticagrelor, expressed his shock and disappointment in an interview with The BMJ. He stated that “there are episodes of skyrocketing rebound and profound platelet inhibition after ticagrelor making patients prone to thrombosis or bleeding.” If doctors had known about these issues during the trials, they would have never started using ticagrelor.

The lack of transparency in AstraZeneca’s research is concerning, especially when coupled with the FDA’s failure to address the problems. The need for accurate and reliable data in healthcare cannot be overstated, as it directly impacts patient care and treatment outcomes. As Serebruany aptly put it, “It’s been obvious for years that there is something wrong with the data. That the FDA’s leadership could look past all these problems…is unconscionable.”

Scientists at the USC Leonard Davis School of Gerontology have made a groundbreaking discovery that sheds light on the unique challenges faced by people with Down syndrome who develop Alzheimer’s disease. Their research reveals a crucial link between high levels of iron in the brain and increased cell damage, providing a potential explanation for why Alzheimer’s symptoms often appear earlier and more severely in individuals with Down syndrome.

Down syndrome is caused by having an extra third copy (trisomy) of chromosome 21, which includes the gene for amyloid precursor protein (APP). People with Down syndrome tend to produce more APP, leading to an increased risk of developing Alzheimer’s disease. In fact, about half of all people with Down syndrome show signs of Alzheimer’s by the age of 60, which is approximately 20 years earlier than in the general population.

The researchers studied donated brain tissue from individuals with Alzheimer’s, those with both Down syndrome and Alzheimer’s (DSAD), and those without either diagnosis. They found that the brains of people with DSAD had twice as much iron and more signs of oxidative damage in cell membranes compared to the brains of individuals with Alzheimer’s alone or those with neither diagnosis.

This excess iron leads to ferroptosis, a type of cell death characterized by iron-dependent lipid peroxidation. In other words, iron builds up, drives the oxidation that damages cell membranes, and overwhelms the cell’s ability to protect itself.

The researchers also discovered that lipid rafts, tiny parts of the brain cell membrane crucial for cell signaling and protein processing, had more oxidative damage and fewer protective enzymes in DSAD brains compared to Alzheimer’s or healthy brains. These lipid rafts showed increased activity of the enzyme β-secretase, which interacts with APP to produce Aβ proteins, potentially promoting the growth of amyloid plaques.

The findings have significant implications for future treatments, especially for people with Down syndrome who are at high risk of Alzheimer’s. Early research in mice suggests that iron-chelating treatments may reduce indicators of Alzheimer’s pathology. Medications that remove iron from the brain or help strengthen antioxidant systems might offer new hope.

The study was supported by various organizations, including the National Institute on Aging and Cure Alzheimer’s Fund. These findings highlight the importance of understanding the biology of Down syndrome for Alzheimer’s research and could lead to new therapeutic approaches for this vulnerable population.

The herpes simplex virus-1 (HSV-1) is a cunning foe that has been infecting humans for centuries. While it’s well-known for causing cold sores, what’s less understood is how this virus hijacks our cells to reproduce itself. A recent study published in Nature Communications reveals the shocking truth: HSV-1 reshapes our genome in three-dimensional space, rearranging its structure to access host genes that help it multiply.

This “opportunistic interior designer” uses its precision to manipulate the human genome, choosing which bits to interact with and exploiting host resources. Researchers at the Center for Genomic Regulation (CRG) in Barcelona made this groundbreaking discovery using super-resolution microscopy and Hi-C techniques, which allowed them to visualize structures as small as 20 nanometers.

Within the first hour of infection, HSV-1 hijacks the human RNA-polymerase II enzyme to synthesize its own proteins. This is followed by the recruitment of topoisomerase I, an enzyme that snips DNA to release torsional stress, and cohesin, a structural protein. Three hours after infection, most polymerase and a sizeable fraction of the other two factors have abandoned human genes.

The consequences are devastating: transcription collapses across the host genome, causing chromatin to compact into a dense shell just 30% of its original volume. This was an unexpected finding, as the structure of chromatin is thought to dictate transcription. The relationship between activity and structure might be a two-way street.

This study has significant implications for public health, especially given the prevalence of HSV-1 worldwide. With nearly four billion people infected, treatments are available only to manage symptoms, while drug-resistant strains are on the rise. There is no cure.

The discovery of topoisomerase I as a potential target for therapy brings new hope. Inhibiting this enzyme stopped infection in cell culture before the virus could make a single new particle. This finding offers a potential new strategy to control HSV-1, which infects nearly four billion people worldwide.

The cold sore virus’ secret is out: it’s not just a harmless nuisance, but a cunning manipulator of our cells that’s been hijacking the human genome in 3D for centuries. The consequences are real, and the time to act is now.