The week’s most astounding developments from the neobiological frontier.

February 1, 2024

The (se)Xist story of autoimmune disease

One longstanding question in women’s health is what accounts for gender disparities in autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and scleroderma? Four times more women suffer from autoimmune diseases in general, and the numbers are far worse with some diseases (in lupus, the ratio is 9-to-1). According to researchers at Stanford University, the answer lies in the X chromosome—or rather on top of it. Men have only one X chromosome (paired with the male Y), but women carry two copies of X. That redundancy could cause dangerously double expression of X chromosome genes, so early in embryonic development, every cell in a growing female fetus shuts down one of their X chromosomes with a long RNA molecule called Xist, which gloms onto one or the other. The Stanford researchers showed in mice that this agglomeration can attract the immune system and drive autoimmunity. In a maddening footnote, the researchers suggest this discovery long eluded scientists because for decades only male cells have been used as reference for studying autoimmunity. But male cells never produce Xist because men never need to suppress their second X chromosome—because they don’t have one! Cell

New pain drug shows promise

Last year, we reported on mixed results of a phase 2 clinical trial of an experimental drug called VX-548, from Boston-based Vertex Pharmaceuticals. The drug targets a human sodium channel protein called Nav1.8, preventing it from transmitting pain signals to the brain—but only at the highest doses tested and often at the cost of side effects like constipation and headaches. Now Vertex is announcing promising phase 3 results from a trial involving 1,118 people. VX-548 was superior to placebo and comparable to opioid-based drugs at alleviating pain—but without the drowsiness and risk of addiction. The results were so good that Vertex plans to submit an NDA (new drug application) to the U.S. Food and Drug Administration in the next six months. If VX-548 hits the market as planned, it will be huge. Some are already predicting it will be a blockbuster drug, exceeding a billion dollars a year in sales, but more significantly it stands to end the suffering of millions of Americans. Press release

Rethinking how we define cancer

For as long as we or any of our readers have been alive, modern society has always defined cancer along crude anatomical lines according to where the primary tumors emerge—breast, prostate, brain, colon, or elsewhere. That division is reflected in everything from the organization of oncology departments, treatment teams, professional societies, and funding streams for federal research, to the activities of activist communities. But in a perspective this week, a group of French doctors is suggesting it may be time to repot the whole plant. Rather than defining cancer in terms of where, a better question to ask would be which—which specific type of cancer is it? They call for redefining cancers in “organ-agnostic” terms according to precision medicine, genetic profiles, molecular characteristics, prognosis, and drug susceptibilities. Doing so would improve our understanding of basic cancer biology, and “classifying cancers according to their molecular characteristics would expedite the access of millions of people to effective treatments,” they write. Nature

The gut cure to viral lung infections

Why do some people who catch COVID-19, RSV, or the flu wind up on life support with severe respiratory infections while others simply go about their day with a few little sniffles? Part of the answer, according to researchers at Georgia State University, is in the gut. Starting with the observation that field mice are more resistant to influenza than their clean-room cousins raised in the lab, they discovered one key difference—their microbiomes. Field mice carry more of a type of segmented filamentous bacteria in their guts, and this bacteria effectively reprograms their lung macrophages, a type of immune cell, which gives them enhanced ability to combat lung viruses. Feeding the same bacteria to laboratory mice gave them greater resistance as well. “These findings demonstrate the potential of gut microbiome to influence the severity of respiratory viral infection,” they write. Cell Host & Microbe

Gut microbiota dictate how cells in the lung known as resident alveolar macrophages (shown with emoji faces here) respond to viral infection. When commensal microbes are present in mice, they reprogram gene expression in the alveolar macrophages, pushing them to engulf and destroy viruses. Courtesy Andrew

Prognostic marker and potential drug target for sepsis

The widespread release of inflammatory chemicals all over the body in response to an infection is called sepsis. It is severe and often deadly, causing multiple-organ failure and one third of all hospital deaths. So serious is this condition that medical centers often form rapid strike teams to sweep in and administer broad-spectrum antibiotics at the first signs of sepsis. Now scientists at Chongqing Medical University in China have identified a molecular marker of sepsis called bone morphogenetic protein 9. Based on a study of 452 people, levels of the protein could be a prognostic marker that could help guide treatment for people with sepsis, improve clinical trials, and may itself be a target for developing specific sepsis treatments. Science Translational Medicine

The kimchi diet

An analysis of 115,726 Korean adults who were 40–69 years old shows that eating three small 50 gram servings of kimchi a day (just over 5 ounces total) is associated with 11 percent lower obesity than eating less than one serving a day. According to researchers at Chung Ang University in Anseong and the World Institute of Kimchi in Gwangju, South Korea, (yes, there is such an organization!) the naturally fermented salt-and-red-pepper-packed pickled wonder is low-calorie, full of dietary fiber, rich in vitamins, and swimming in gut-friendly lactic acid bacteria. You may hold your nose when jars of the fermented cabbage are opened, but we say: Bring it! BMJ Open

Don’t bogart that bone, my friend!

In an anonymous online survey of more than 2,000 people in Denmark, researchers at the University of Copenhagen have discovered that 38 percent of Danish dog owners feed their dogs unlicensed marijuana products. In Denmark, it is illegal for veterinarians to prescribe cannabis or cannabinoid supplements, and there are no doggie dispensaries. That doesn’t stop people, apparently, from purchasing products online and feeding them to their animals for things like pain and behavioral issues. “This supports the need for more evidence-based knowledge in veterinary cannabinoid therapy,” the researchers write. PLOS ONE

In Denmark, 38 percent of dog owners give their pets unlicensed cannabis products. Pernille Holst, CC-BY 4.0