Scientists Zoom In on Genetic Causes of Inflammatory Bowel Disease

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iStock

Study by study, researchers are pushing ever closer toward identifying the gene variants to blame for inflammatory bowel disease (IBD). The latest and most promising findings were published in the journal Nature.

There are two forms of IBD: ulcerative colitis, which affects only the colon and is more common in women; and Crohn's disease, which can affect any part of the gastrointestinal tract and is slightly more common in men. Today, IBD affects between 1 and 1.3 million Americans, yet we understand very little about why it happens or why some groups of people are more susceptible than others.

It's possible and even likely, scientists say, that the root of the illness could lie in our genes. Previous studies have linked IBD to hundreds of different genetic variants, but that's as specific as they could get.

To take a closer look, researchers at three institutions collaborated to build a massive, high-resolution genetic map. They collected the genomes of 67,852 different people—18,967 with Crohn's disease, 14,628 with ulcerative colitis, and 34,257 healthy people for a control group—and combed through, looking for variants unique to the folks with IBD.

Like previous researchers, they found plenty. But the new map was so detailed that its creators could zoom in further and further down, checking how likely it was that any given variant could actually cause the disease. From hundreds, they narrowed it down to just 18 variants, and had at least 95 percent certainty that these were the ones responsible. Some of these gene variants were related to processing amino acids; some seemed to interfere with healthy molecule binding; and some were tied to the switching on and off of immune or gut cells.

"We need to be careful in deciding when we are sure we have the right variant," first author Hailiang Huang, of Massachusetts General Hospital and the Broad Institute, said in a statement. "This new technique helps us to pinpoint which genetic variants are implicated in IBD with greater confidence."

The authors say that isolating IBD-related gene variants will help develop new drugs, and could someday even aid in personalized medicine by helping doctors identify which existing drugs will be most effective for their patients.

Why Does Scratching Make Itching Worse?

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iStock/champja

It feels like a biological blooper: A persistent itch is made worse by scratching, the one thing that provides instantaneous relief. Evolutionary biologists have proposed that the relationship between scratching and itching developed when disease-carrying parasites and insects bit humans, causing itching skin; scratching brushed the bugs away. Anyone suffering from a mosquito bite can understand that connection.

There’s no simple answer for why skin that has just been scratched becomes even itchier, but researchers have identified some mechanisms behind the irritating phenomenon.

Why Scratching an Itch Doesn't Help

Our sensory neurons are constantly bombarded with stimuli, so some sensations take precedence over others. Sensory signals of one type can be overridden by signals of other types if the latter are strong enough. The overridden signals don’t even reach the brain—they’re stopped by specific neurons in the spinal cord. In this way, the pain caused by scratching is often sufficient to drown out the itch—but only temporarily.

Cells in the brain stem produce the neurotransmitter serotonin, which quells pain. But according to Zhou-Feng Chen, Ph.D., director of the Center for the Study of Itch at Washington University School of Medicine in St. Louis, Missouri, serotonin has an additional function. His group has found that as the serotonin spreads through the spinal cord, it can activate neurons that transmit itch signals to the brain, compelling us to scratch even more.

Each time we scratch, we put this cycle in motion. The increasing amount of serotonin may even make us scratch harder, until the urge to scratch becomes detached from any itch trigger on the skin. “It’s to try to suppress the itchy sensation, which occurs in your brain,” Chen tells Mental Floss. By this mechanism, itches can even become chronic.

Serotonin signaling isn’t the only way scratching worsens an itch; harm to the skin caused by scratching is another contributor. “When the skin barrier is irritated or further damaged, it releases certain pro-inflammatory factors that can directly aggravate itch by stimulating the sensory nerve fibers,” Brian Kim, M.D., co-director of the Center for the Study of Itch, tells Mental Floss. Those factors can also activate your immune system, and some types of immune cells around the affected area may produce chemicals that induce itch.

The very idea of scratching can also be a trigger. Chen’s research group reported last year that mice appear susceptible to scratching when they see other mice do the same. “Itching is actually contagious between people, between animals, and in your body itself,” Chen says. “When you scratch one place, you quickly want to scratch another area.” Scratching doesn’t just make itch more intense—it sometimes also causes the sensation to spread.

Relief for Itching

In mild cases, it may be possible to resist scratching through sheer force of will—but that’s not usually a long-term solution.

“I always feel bad because a lot of people say to patients, ‘Don’t scratch, don’t scratch,’ but that’s very challenging,” Kim tells Mental Floss. He says he tries to determine the cause of a person’s itchiness first. If it’s caused by an underlying medical problem, such as infestation with lice or liver disease, managing that issue may resolve the itch. Even if the underlying problem can’t be cured, there are medications that can calm itch in certain circumstances, such as antihistamines for allergy-induced itch and topical corticosteroids for itch caused by certain skin conditions, including eczema.

For now, drugs like these may be our best weapons against itching. “I think itch is often viewed as quirky, not serious, or embarrassing,” Kim says, which explains why there’s little research on itch despite its impact on our lives. Unfortunately, that coveted scratch in a bottle remains out of reach.

A Generic EpiPen Coming in Early 2019 Could Save You Money

Brand-name EpiPens at a Congressional hearing on the escalating cost of the drug in 2016
Brand-name EpiPens at a Congressional hearing on the escalating cost of the drug in 2016
Alex Wong/Getty Images

For an incredibly common, life-saving medication, EpiPens (epinephrine auto-injectors) are surprisingly difficult for many consumers to get ahold of. Their cost has skyrocketed in recent years from less than $100 for a pack of two to more than $600. They’ve gotten so expensive that some EMTs have resorted to using syringes to manually administer epinephrine rather than purchasing the standard auto-injectors, which are almost exclusively made by the pharmaceutical company Mylan. Generic options have been slow to come to market, but according to Business Insider, a recently approved EpiPen rival is coming in the first few months of 2019, and it could save consumers a significant chunk of change.

The drug’s developers have had an unusually hard time getting the new EpiPen alternative, called Symjepi, onto store shelves. The drug was approved in 2017, but the company, Adamis Pharmaceuticals, had trouble finding investors. Now, Novartis, the Swiss-based pharmaceutical giant that manufactures drugs like Ritalin, is releasing the drug through its Sandoz division (perhaps most famous for it role in discovering LSD in the 1930s).

Symjepi will cost $250 out-of-pocket for a pack of two doses. That’s 16.6 percent less than the Mylan-authorized generic EpiPen or Teva’s generic EpiPen, which both sell for $300. It differs a bit from its rivals, though, in that it’s a pre-filled, single-dose syringe rather than a spring-loaded auto-injector. Auto-injectors are plastic, pen-like devices that keep the needle shielded until the moment of injection, and are specifically designed to help make it easier for untrained (even squeamish) people to use in an emergency. With this version, patients will need to remove a needle cap and inject the needle. Just like the EpiPen, though, it’s designed to be injected in the upper thigh, through clothing if necessary.

If you have health insurance, the difference in cost may not matter as much for you as a consumer, depending on your plan. (I personally picked up a two-pack of Mylan-authorized generic Epipens at CVS recently for $0, using a manufacturer’s Epipen coupon to knock down what would have been a $10 copay.) But it will matter considerably for those with high-deductible plans and to insurers, which, when faced with high costs, eventually pass those costs on to the consumer either through higher co-pays or higher premiums. It also affects agencies that buy EpiPens for emergency use, like local fire departments. And since EpiPens expire after just a year, the costs add up.

However, there’s currently a shortage of EpiPens on the market, according to the FDA, making it more important than ever to have other epinephrine drugs available to those at risk for serious allergic reactions.

[h/t Business Insider]

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