Common NSAID Used for Period Pain May Reverse Memory Loss in Alzheimer’s


Alzheimer’s drug research continues to look to the future, toward new drugs that might one day treat the ravaging symptoms of the neurodegenerative disease, such as memory loss and even lead to a cure. However, a research team out of the University of Manchester in the UK, led by neuroimmunologist David Brough, has taken their work in the opposite direction, looking at old drugs that are successfully reversing memory loss in a mouse model. Their findings were published in the journal Nature Communications.

When it comes to understanding what causes the dangerous buildup of amyloid plaques and tau tangles in the brain that are prevalent in Alzheimer’s, “evidence is building for inflammation," neuroimmunologist Jack Rivers-Auty, a co-author on the paper, tells mental_floss. "It’s a bit like when you roll your ankle—you put ice on it to reduce swelling because you’re worried about inflammation causing more damage," he says. "Inflammation is a very complex process made up of many cell types and proteins… many of which may be causing collateral damage in the brain."

He and neuroimmunology colleague Mike Daniels conducted experiments on mice after their lab director theorized that common non-steroidal anti-inflammatory drugs (NSAIDs) might inhibit a key inflammatory pathway in the brain that damages brain cells, called the NLRP3 inflammasome complex. “I screened a number of drugs against the inflammasome with cells in a dish,” Daniels tells mental_floss. He was expecting ibuprofen and other more well-known drugs to be the most potent, but in fact, “they had no effect,” he says.

What did work was a less commonly known NSAID called mefanimic acid, which is mainly used for menstrual pain, he says. It worked because it has a different structure. Classic NSAIDs inhibit a protein called cyclooxygenase, whereas mefanimic acid inhibits the inflammasome complex itself.

Next they tested the drugs in a double-blind, placebo-controlled study on mice that were at an age when memory deficits begin to show up, approximately 15 months old. Rivers-Auty says if they were to translate this into a clinical setting with humans, “we would want to aim for people who have just started Alzheimer’s disease. Alzheimer’s [partly causes] the death of neurons, and it’s hard to grow new neurons.”

They used a range of memory tests on the mice to determine whether their memory was in decline before administering mefanimic acid. The most common among them is called the novel object recognition test. This test is useful because mice, like us, are sensitive to unfamiliar objects. Imagine you enter a parking lot looking for your car. In the lot, you find only two objects: your car and an alien's spaceship. "You would spend more time exploring the spaceship because you hadn’t seen it before,” Rivers-Auty says.

Mice will behave similarly. But what happens if their memory is deficient? To find out, the team gave 10 mice a placebo, while the other 10 were treated with mefanimic acid via a subcutaneous pump for 28 days. The study found that “the mouse with good memory explores the new object, and the mouse with poor memory explores them both,” Rivers-Auty explains. 

At the end of the study, the mice that had been given the mefanimic acid “did not have memory deficits,” he says. The drug had restored memory function to the mice with failing memory.

The results were so surprising to them, Rivers-Auty says, “We were literally hooting and hollering. We couldn’t believe how well it worked. It’s very unusual for groups to reverse memory deficits.”

The team is hopeful that this discovery could bypass as much as 15 years of the usual process to develop a new drug because mefanimic acid is already in use by humans and has been deemed safe. “We can skip the extensive animal testing and the first stage of human trials,” says Rivers-Auty. “This saves a huge amount of time and money.”

However enthusiastic he and his colleagues are about their results, Rivers-Auty is skeptical that the team will find commercial funding sources for the next stage of trials in humans because “pharmaceutical companies who usually fund these studies have no interest in funding a study they can’t make money off,” he says. Instead, this team relies on charities such as the Alzheimer’s Society and Alzheimer’s Research UK, which funded their work.

Karen Bleier, AFP/Getty Images
Bill and Melinda Gates Will Repay Nigeria's $76 Million Polio-Fighting Loan
Karen Bleier, AFP/Getty Images
Karen Bleier, AFP/Getty Images

Not long after announcing a $100 million donation to find a cure for Alzheimer's disease, Bill and Melinda Gates have agreed to pay off Japan's $76 million loan to Nigeria to stamp out polio, Quartz reports.

Polio has been eradicated in most countries around the world, but it's still present in Nigeria, as well as in Afghanistan and Pakistan. In 2008, according to The Conversation, Nigeria accounted for 86 percent of all polio cases in Africa. This high number was thanks in part to low immunization rates and calls from extremists to boycott polio vaccinations out of fear that they were tainted with anti-fertility steroids.

National and international campaigns were launched to lower polio rates in Nigeria, and in 2014 the nation received the loan from Japan to boost disease-fighting efforts. Progress has been made since then, with no new cases of polio reported in Nigeria in 2017. Two children had contracted polio in 2016, two years after Nigeria's last known case.

Nigeria's loan repayments to Japan were slated to begin in 2018. The Bill & Melinda Gates Foundation agreed to cover the costs after Nigeria met its goal of "achieving more than 80 percent vaccination coverage in at least one round each year in very high risk areas across 80 percent of the country's local government areas," Quartz reports. The loan will be repaid over the next 20 years.

While the Gates Foundation is lending a hand to Nigeria, the Associated Press reports that health officials in Pakistan's eastern Punjab province recently launched a new chapter in the nation's ongoing struggle against the disease. Health workers will engage in a week-long, door-to-door vaccination campaign, though efforts like this are risky due to threats from the Taliban and other militant groups, who view vaccinations as a Western conspiracy and believe they sterilize children. Anti-polio efforts in Pakistan also suffered after the CIA used vaccinations as a cover to get DNA samples from the Bin Laden compound.

[h/t Quartz]

Stones, Bones, and Wrecks
8 Amazing Things Discovered During the Expansion of the London Underground

In 2009, the city of London embarked on a massive infrastructure project: a 73-mile underground railway network called the Elizabeth Line that will ultimately boost urban train capacity by 10 percent. Slated to be up and running by 2018, the undertaking allowed archaeologists to take an unprecedented peek at swathes of subterranean London, and yielded plenty of cool historic treasures from various periods. Here's a small sampling of the finds.


A skeleton belonging to a victim of the Black Plague, unearthed by archaeologists while expanding the London Underground.

While excavating London's Charterhouse Square in 2013, archaeologists unearthed dozens of skeletons. Scientists analyzed the remains and discovered that some of them belonged to victims of the Black Death—a.k.a. bubonic plague—who succumbed to pandemics that swept 14th- and 15th-century England.

Teeth contained traces of DNA from the plague bacterium Yersinia pestis, and radio-carbon dating indicated that the burial ground had been used during two outbreaks of plague, one from 1348 to 1350 and another during the 1430s. The skeletons also showed signs of poor diets and hard lifestyles, which might have been contributing factors for why Londoners were so susceptible to the plague.

But the so-called plague pit didn't just contain those who'd succumbed to disease. Not only were some bodies plague-free, "what they found was, not bodies tumbled together as they'd expected, but rather orderly burials with people laid in rows with their bodies orientated in one direction," historian Gillian Tindall told The Guardian. This suggests not all of them died due to plague but from other, more everyday causes.


An 8000-year-old piece of flint, discovered by archaeologists while expanding the London Underground.

While digging at North Woolrich, in southeast London, archaeologists discovered a Mesolithic-era site along the Thames where early humans are thought to have crafted tools around 8500 to 6000 years ago. The encampment had traces of campfires and flint scatters, and experts recovered 150 pieces of flint, including an 8000-year-old stone tool.

"This is a unique and exciting find that reveals evidence of humans returning to England and in particular the Thames Valley after a long hiatus during the Ice Age," Crossrail lead archaeologist Jay Carver said in a news release. "It is one of a handful of archaeology sites uncovered that confirms humans lived in the Thames Valley at this time. The concentration of flint pieces shows that this was an exceptionally important location for sourcing materials to make tools that were used by early Londoners who lived and hunted on Thames Estuary islands."


A bawdy Victorian chamber pot, discovered by archaeologists while excavating future London Underground sites.

While excavating the Stepney Green station in East London, archaeologists came across a 19th-century cesspit dating to sometime after 1850. The waste hole was filled with tobacco pipes and fragments of pots, including a raunchy Victorian chamber pot. It was once likely kept under a bed, and allowed for its owner to do their business in private during the evening hours.

The pot's bottom contains a cartoon of a grimacing man, encircled by the phrase "Oh what I see/I will not tell." Witty cursive lines once covered the exterior of the broken vessel. Archaeologists were able to decipher one line, which read "… when you in it want to p-s/ Remember they who gave you this."


A Tudor-era bowling or skittles bowl, discovered by archaeologists while excavating future sites for the London Underground's expansion.

In addition to the aforementioned cesspit, excavations at Stepney Green also revealed a 15th-century Tudor manor house, complete with moat. Originally home to a rich family named Fenne, it was once called King John's Court or Palace, and later became known as the Worcester House after its owner the Marquis of Worcester.

In 2013, archaeologists excavated the home's foundations, moat, and boundary walls. Inside the moat they discovered a wooden ball made from willow, which was likely either used for bowling or skittles, a European lawn game. Other recovered items included fine glassware, tableware, and cooking and storage vessels, all of which were buried when the moat was either destroyed or filled in.


55-million-year-old amber, retrieved by engineers while expanding the London Underground

Slated to open in late 2018, London's new Canary Wharf business district station is located deep below a mixed-use development called Crossrail Place. While tunneling at Canary Wharf was too deep to disturb any buried relics, engineers were still able to retrieve a piece of 55-million-year-old amber from nearly 50 feet below the site's dock bed before construction began. It's the oldest amber to have ever been found in London, and is also notable considering that amber isn't often found in the UK to begin with.

Amber, or fossilized tree resin, takes millions of years and proper burial conditions to form. These preserved relics often contain prehistoric plants and creatures, suspended in the clear material. Experts said they plan to analyze the Canary Wharf amber to learn more about prehistoric environmental conditions and vegetation. The fossil also contained bubbles of trapped gas, which scientists said might yield new scientific insights about global warming.


A rare Roman medallion dating back to 245 CE, found by archaeologists during the London Underground expansion.

Archaeologists excavating Crossrail's Liverpool Street site discovered more than 100 mostly-copper Roman coins, along with a handful of silver currency. They ranged in date from 43 CE, during the reign of Emperor Claudius, to 348 CE.

One of the most exciting discoveries among these coins was a rare bronze medallion that was issued to mark the New Year in 245 CE. Presented by Emperor Phillip I (also called Philip the Arab) to a high-ranking government official, it's only the second example of its kind that's ever been found, according to The Guardian.

"You wonder how it got there, who brought it with them, and then how did they lose it—were they heartbroken?" speculated Jackie Keily, a curator at the Museum of London who organized an exhibition of 500 Crossrail artifacts in 2017.


A Roman skull, uncovered by archaeologists during the expansion of the London Underground.

In 2013, Crossrail workers found Roman pottery and around 20 Roman skulls while working on the Liverpool Street station site. Other Roman skulls had been found in the area, along the historic River Walbrook, and some speculated that they belonged to rebels led by the Iceni warrior-queen Boudicca, who revolted against the Roman Empire during the 1st century CE. But since the newly unearthed skulls were found in sediment that had accumulated in a bend of the river, archaeologists believe that they likely washed out of an eroded Roman cemetery long ago. Moreover, the skulls appear to date to after the uprising.


The gravestone of plague victim Mary Godfree, discovered at Liverpool Street in London during the Crossrail excavations.

On September 2, 1665, a girl named Mary Godfree succumbed to the plague—one of 95 people from the same church parish who died from the disease that day. She was remembered solely by a line in a burial register until October 2015, when archaeologists discovered her limestone burial stone while excavating the new Liverpool Street Crossrail station site.

The area was originally home to the historic New Churchyard burial ground, also called the Bedlam burial ground. There, archaeologists discovered a mass grave, along with the remnants of 10 stone markers. Godfree's headstone didn't mark the presence of her actual grave, as the headstone had been removed sometime during the 18th century and reused in the foundation of a wall. Still, it revealed new insights into how and where the rediscovered Londoner was buried, and what burial conditions were like during the Great Plague.


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