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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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Medicine
Why Haven't We Cured Cancer Yet?
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Walkathons, fundraisers, and ribbon-shaped bumper stickers raise research dollars and boost spirits, but cancer—the dreaded disease that affects more than 14 million people and their families at any given time—still remains bereft of a cure.

Why? For starters, cancer isn't just one disease—it's more than 100 of them, with different causes. This makes it impossible to treat each one using a one-size-fits-all method. Secondly, scientists use lab-grown cell lines cultivated from human tumors to develop cancer therapies. Living masses are far more complex, so potential treatments that show promise in lab experiments often don't work on cancer patients. As for the tumors themselves, they're prone to tiny genetic mutations, so just one growth might contain multiple types of cancer cells, and even unique sub-clones of tumors. These distinct entities might not respond the same way, or at all, to the same drug.

These are just a few of the challenges that cancer researchers face—but the good news is that they're working to beat all of them, as this TED-Ed video explains below.

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Health
Skipping Breakfast Could Be Bad for Your Heart
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There are mountains of evidence supporting the claim that breakfast really is the most important meal of the day. Getting something in your stomach in the first hours of the morning can regulate your glucose levels, improve your cognition, and keep your hunger in check. Now new research published in the Journal of the American College of Cardiology points to another reason not to wait until lunchtime to break last night’s fast. As TIME reports, people who skip breakfast are at an increased risk for atherosclerosis, a disease caused by plaque buildup in the arteries.

Researchers surveyed over 4000 men and women between the ages of 40 and 54 living in Spain. After looking at the dietary habits of each participant, they broke them into three groups: people who consumed more than 20 percent of their daily calories in the morning; those who got 5 to 20 percent; and those who ate less than 5 percent.

The subjects who ate very little in the a.m. hours or skipped breakfast all together were 2.5 more likely to have generalized atherosclerosis. This meant that plaque was starting to collect on the walls of their arteries, hardening and narrowing them and increasing the risk for heart attack or stroke. People who fell into the 5 to 20 percent calorie category were also more likely to show early signs of the disease, while those who ate the most calories in the morning were the healthiest.

These results aren’t entirely surprising. Previous studies have shown a connection between skipping breakfast and health problems like high blood pressure, high cholesterol, diabetes, and unwanted weight gain. A possible explanation for this trend could be that waiting several hours after waking up to eat your first meal of the day could trigger hormonal imbalances. The time between getting into and out of bed is the longest most of us go without eating, and our bodies expect us to consume some calories to help kickstart our energy for the day (drinking straight coffee doesn’t cut it). Another theory is that people who don’t eat in the morning are so hungry by the time lunch rolls around that they overcompensate for those missing calories, which is why skipping breakfast doesn’t make sense as a diet strategy.

But of course there are many breakfast skippers who aren’t motivated by health reasons either way: They just don’t think they have the time or energy to feed themselves in the morning before walking out the door. If this describes you, here are some simple, protein-packed meals you can prepare the night before.

[h/t TIME]

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