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New Therapy Treats Autoimmune Disease Without Suppressing Immune System

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Treatments for autoimmune diseases are hampered by a lack of understanding of specific immune cells at work in individual diseases. The first line of treatment is immune suppressants, like steroids or drugs often given to transplant recipients, which suppress all immune cells and leave the patient at increased risk of infection and cancers.

Now, promising new research from the Perelman School of Medicine at the University of Pennsylvania (UPenn) has found a way to target a specific subset of antibody-making cells in a rare autoimmune disease called pemphigus vulgaris (PV) without suppressing healthy immunity. The research, published recently in Science, could open the door to targeting other autoimmune diseases.

Autoimmune research is “stuck in the same dark ages as cancer therapy was decades ago, where they had no way of targeting cancer cells, so they just targeted all dividing cells,” study author Aimee S. Payne, an associate professor of dermatology at UPenn, tells mental_floss.

In PV, which causes blisters and sores in mucous membranes, a kind of immune cell called B cells attack a protein called desmoglein-3 (Dsg3), which typically helps skin cells adhere together. Until the advent of steroids and a drug therapy called Rituximab, the disease was usually fatal. “Now patients are no longer dying from the disease, which is good, but they have a lot of complications from the therapies,” Payne says.

Payne and her co-senior author Michael Milone adapted their autoimmune technique from an anti-cancer therapy called chimeric antigen receptor therapy, or CAR, in which T cells are engineered to kill cancerous cells in some leukemias and lymphomas. The cancer CAR therapy has been successful in human trials, though with some side effects. Payne’s team’s version is called CAART (chimeric autoantibody receptor therapy). The team designed an artificial CAR-type receptor in a mouse model that acts as “bait” to only those B cells producing the anti-Dsg3 antibodies, by attracting them to the engineered receptors and killing only them, and no other cells. They were able to successfully kill the Dsg3 cells without any symptoms of blistering or autoimmunity in the animals.

“The power of the CAR technology in general is that it has incredible specificity and potency at killing just what it’s designed to kill,” Payne says.

While CAR T cell therapy in cancer can cause a painful, almost sepsis-like syndrome called Cytokine Release Syndrome, Payne is confident that CAART will not be likely to cause this same condition in patients, because it is only targeting a very specific subset of B cells. “We’re not killing all of the B cells, only a small fraction of them. We think that in patients with active diseases, we’d be killing maybe at most one percent of your total B cells, the critical ones that are causing disease.”

Though Payne feels they have showed the “proof of concept” as well as cancer CAR therapy did before going to human trials, they will be attempting to cure dogs with the disease before moving on to human trials.

What they’ve learned from treating PV with this new autoimmune therapy will act “as a paradigm for all of the other auto-antibody mediated diseases,” Payne says. Not only is she hopeful about the future of treating autoimmune disease, but she sees this as another drop in the bucket of “personalized medicine” in which scientists will use genotyping to develop personalized therapies for a person’s disease “rather than treating everybody with a one-size-fits-all approach.” 

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Emery Smith
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Stones, Bones, and Wrecks
The 'Alien' Mummy Is of Course Human—And Yet, Still Unusual
Emery Smith
Emery Smith

Ata has never been an alien, but she's always been an enigma. Discovered in 2003 in a leather pouch near an abandoned mining town in Chile's Atacama Desert, the tiny, 6-inch mummy's unusual features—including a narrow, sloped head, angled eyes, missing ribs, and oddly dense bones—had both the “It's aliens!” crowd and paleopathologists intrigued. Now, a team of researchers from Stanford University School of Medicine and UC-San Francisco has completed a deep genomic analysis that reveals why Ata looks as she does.

As they lay out in a paper published this week in Genome Research, the researchers found a host of genetic mutations that doomed the fetus—some of which have never been seen before.

Stanford professor of microbiology and immunology Garry Nolan first analyzed Ata back in 2012; the mummy had been purchased by a Spanish businessman and studied by a doctor named Steven Greer, who made her a star of his UFO/ET conspiracy movie Sirius. Nolan was also given a sample of her bone marrow; his DNA analysis confirmed she was, of course, human. But Nolan's study, published in the journal Science, also found something very odd: Though she was just 6 inches long when she died—a typical size for a midterm fetus—her bones appeared to be 6 to 8 years old. This did not lead Nolan to hypothesize an alien origin for Ata, but to infer that she may have had a rare bone disorder.

The current analysis confirmed that interpretation. The researchers found 40 mutations in several genes that govern bone development; these mutations have been linked to "diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia)," they write. The latter is commonly known as dwarfism. Some of these mutations are linked to conditions including Ehlers-Danlos syndrome, which affects connective tissue, and Kabuki syndrome, which causes a range of physical deformities and cognitive issues. Other mutations known to cause disease had never before been associated with bone growth or developmental disorders until being discovered in Ata.

scientist measures the the 6-inch-long mummy called Ata, which is not an alien
Emery Smith

"Given the size of the specimen and the severity of the mutations … it seems likely the specimen was a pre-term birth," they write. "While we can only speculate as to the cause for multiple mutations in Ata's genome, the specimen was found in La Noria, one of the Atacama Desert's many abandoned nitrate mining towns, which suggests a possible role for prenatal nitrate exposure leading to DNA damage."

Though the researchers haven't identified the exact age of Ata's remains, they're estimated to be less than 500 years old (and potentially as young as 40 years old). Genomic analysis also confirms that Ata is very much not only an Earthling, but a local; her DNA is a nearest match to three individuals from the Chilote people of Chile.

In a press statement, study co-lead Atul Butte, director of the Institute for Computational Health Sciences at UC-San Francisco, stressed the potential applications of the study to genetic disorders. "For me, what really came of this study was the idea that we shouldn't stop investigating when we find one gene that might explain a symptom. It could be multiple things going wrong, and it's worth getting a full explanation, especially as we head closer and closer to gene therapy," Butte said. "We could presumably one day fix some of these disorders."

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Health
Just Two Cans of Soda a Day May Double Your Risk of Death From Heart Disease
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If you've been stocking your refrigerator full of carbonated corn syrup in anticipation of warmer weather, the American Heart Association has some bad news. The advocacy group on Wednesday released results of research that demonstrate a link between consumption of sugary drinks—including soda, fruit juices, and other sweetened beverages—and an increased risk of dying from heart disease.

Study participants who reported consuming 24 ounces or more of sugary drinks per day had twice the risk of death from coronary artery disease of those who averaged less than 1 ounce daily. There was also an increased risk of death overall, including from other cardiovascular conditions.

The study, led by Emory University professor Jean Welsh, examined data taken from a longitudinal study of 17,930 adults over the age of 45 with no previous history of heart disease, stroke, or diabetes. Researchers followed participants for six years, and examined death records to determine causes. They observed a greater risk of death associated with sugary drinks even when they controlled for other factors, including race, income, education, smoking habits, and physical activity. The study does not show cause and effect, the researchers said, but does illuminate a trend.

The study also noted that while it showed an increased risk of death from heart disease, consumption of sugary foods was not shown to carry similar risk. One possible explanation is that the body metabolizes the sugars differently: Solid foods carry other nutrients, like fat and protein, that slow metabolism, while sugary drinks provide an undiluted influx of carbohydrates that the body must process.

The news will likely prove troublesome for the beverage industry, which has long contended with concerns that sugary drinks contribute to type 2 diabetes and tooth decay. Some cities, including Seattle, have introduced controversial "soda tax" plans that raise the sales tax on the drinks in an effort to discourage consumption.

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