Diabetes Drug May Have Potential to Treat Parkinson’s Disease

While further research is needed, it’s another example of how powerful drug research can be. Now if only the U.S. spent more of this kind of research instead of inefficiently giving too much of it to the pharmaceutical industry.

A drug commonly used to treat diabetes may have disease-modifying potential to treat Parkinson’s disease, a new study suggests, paving the way for further research to define its efficacy and safety.

The study, published in The Lancet and funded by The Michael J. Fox Foundation for Parkinson’s Research (MJFF), found that people with Parkinson’s who injected themselves each week with exenatide for one year performed better in movement (motor) tests than those who injected a placebo.

“This is a very promising finding, as the drug holds potential to affect the course of the disease itself, and not merely the symptoms,” said the study’s senior author, Professor Tom Foltynie (UCL Institute of Neurology). “With existing treatments, we can relieve most of the symptoms for some years, but the disease continues to worsen.”

The researchers followed 60 people with Parkinson’s disease at the National Hospital for Neurology and Neurosurgery (NHNN) as they used either a once-weekly injection of exenatide for 48 weeks, or a placebo, in addition to their regular medications.

They found that people who used exenatide had better motor function at 48 weeks when they came off the treatment, which persisted after the 12-week follow-up. Those who had injected the placebo showed a decline in their motor scores at both the 48- and 60-week tests. The advantage of 4 points, on a 132-point scale of measures such as tremors, agility and speech, was statistically significant.

The participants did not report noticeable improvements in their symptoms during the trial period beyond what their standard medication already did for them. They were tested while temporarily off all medication, to determine how the disease itself was progressing. The research did not determine conclusively whether the drug was modifying the disease itself, so the next stage in the research will investigate that more fully.

Parkinson’s disease affects 1 in 500 people and is the second most common neurodegenerative disease worldwide. Symptoms typically don’t become apparent until over 70% of the brain’s dopamine-producing cells have been affected. The condition results in muscle stiffness, slowness of movement, tremors, sleep disturbance, chronic fatigue and an impaired quality of life.

The above is from August 2017. Update on related Parkinson’s research on August 10th, 2018:

In July 2018, Johns Hopkins researchers developed an experimental drug that slows Parkinson’s disease in mice.

Johns Hopkins researchers say they have developed an experimental drug, similar to compounds used to treat diabetes, that slows the progression of Parkinson’s disease itself — as well as its symptoms — in mice. In experiments performed with cultures of human brain cells and live mouse models, they report the drug blocked the degradation of brain cells that is the hallmark of Parkinson’s disease. The drug is expected to move to clinical trials this year.

“It is amazingly protective of target nerve cells,” says Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Dawson explains that if planned clinical trials for the drug, named NLY01, are successful in humans, it could be one of the first treatments to directly target the progression of Parkinson’s disease, not just the muscle rigidity, spasmodic movements, fatigue, dizziness, dementia and other symptoms of the disorder.

A report of the study’s results was published June 11 in Nature Medicine.

According to the investigators, NLY01 works by binding to so-called glucagon-like peptide-1 receptors on the surface of certain cells. Similar drugs are used widely in the treatment of type 2 diabetes to increase insulin levels in the blood. Though past studies in animals suggested the neuroprotective potential of this class of drugs, researchers had not shown directly how it operated in the brain.

To find out, Dawson and his team tested NLY01 on three major cell types in the human brain: astrocytes, microglia and neurons. They found that microglia, a brain cell type that sends signals throughout the central nervous system in response to infection or injury, had the most sites for NLY01 to bind to — two times higher than the other cell types, and 10 times higher in humans with Parkinson’s disease compared to humans without the disease.

Dawson and his team knew that microglia secreted chemical signals that converted astrocytes — the star shaped cells that help neurons communicate with their neighbors — into aggressive “activated” astrocytes, which eat away at the connections between cells in the brain, causing neurons to die off. They speculated that NLY01 might stop this conversion.

“The activated astrocytes we focused on go into a revolt against the brain,” says Dawson, “and this structural breakdown contributes to the dead zones of brain tissue found in those with Parkinson’s disease. The ideas was that if we could find a way to calm those astrocytes, we might be able to slow the progression of Parkinson’s disease.”

In a preliminary experiment in laboratory-grown human brain cells, Dawson’s team treated human microglia with NLY01 and found that they were able to turn the activating signals off. When healthy astrocytes were combined with the treated microglia, they did not convert into destructive activated astrocytes and remained healthy neuroprotective cells. Dawson’s team suspected that neurons throughout the body could be protected in the same way.

They explored this hypothesis by testing the drug’s effectiveness in mice engineered to have a rodent version of Parkinson’s disease.

In one experiment, Dawson’s team injected the mice with alpha-synuclein, the protein known to be the primary driver of Parkinson’s disease, and treatedmice with NLY01. Similar but untreated mice injected with alpha-synuclein showed pronounced motor impairment over the course of six months in behavioral tests such as the pole test, which allows researchers to measure motor impairment such as that caused by Parkinson’s disease. However, Dawson’s team found that the mice treated with NLY01 maintained normal physical function and had no loss of dopamine neurons, indicating that the drug protected against the development of Parkinson’s disease.

In a second experiment, Dawson’s team used mice that were genetically engineered to naturally produce more human-type alpha-synuclein typically used to model human Parkinson’s disease that runs in families. Under normal conditions, these so-called transgenic mice will succumb to the disease in 387 days. However, Dawson’s team found that treatment with NLY01 extended the lives of the 20 mice treated with the drug by over 120 days.

Upon further investigation, Dawson’s team found that the brains of the mice treated with NLY01 showed few signs of the neurodegenerative characteristics of Parkinson’s disease.

Parkinson’s disease is a progressive disorder of the nervous system that affects approximately 1 million people in the U.S., according to the Parkinson’s Foundation. Early symptoms include tremors, trouble sleeping, constipation and trouble moving or walking, which ultimately give way to more severe symptoms such as loss of motor function and the ability to speak, and dementia. Most people begin showing symptoms in their 60s, but cases have been reported in patients as young as 2 years old.

Dawson cautions that the experimental drug must still be tested for safety as well as effectiveness in people, but based on the safety profile of other similar drugs, he does not anticipate any major roadblocks to its use in humans.

Dawson says he and his team have reason to be hopeful that NLY01 could, in a relatively short period of time, make an impact on the lives of those with Parkinson’s.

Similar drugs to NLY01 already approved by the Food and Drug Administration for the treatment of type 2 diabetes include exenatide, lixisenatide, liraglutide and dulaglutide, each of which can cost approximately $2,000 for a 90-day supply. NLY01 is a long-acting drug with improved the brain penetration compared to these approved drugs for diabetes.

Considerations for Securing and Optimizing the Internet of Things

Devices from smartphones to wifi-connected refrigerators represents what’s called the “Internet of Things,” billions of devices that are connected to the Internet. As the number of devices with Internet connectivity is set to expand significantly in the near future, it is worth examining how to best use the IoT for the future.

It is first of all worth noting that there will be numerous security vulnerabilities opened for consumers because of the expansion of the Internet of Things. Of the tens of billions of devices that will be added over the next several years, few of them will likely have regular security updates.

Security updates are important in computer security because they allow for vulnerabilities in software to be patched. While vulnerabilities in devices are known and persist as unpatched, it creates opportunities for adversaries to exploit them.

Billions of new vulnerabilities create problems because the way computer security tends to work, it may only one vulnerability on a network to compromise much else. That’s part of why defense in computer security has been so difficult — the attacker may only need one opening, while the defender may have to defend everything.

For example, say an adversary manages to compromise someone’s phone. The phone may then later connect to the refrigerator to prepare refreshments, further allowing the spread of malicious software from one infected device to another. This process may repeat itself again if the refrigerator were able to compromise the Internet-connected router, and once the router is compromised, the thermostat could be compromised too, making a home too hot or cold while driving up electricity costs.

There are a variety of realistic enough scenarios like this, which are more concerning when more sensitive items such as computers accessing bank accounts and home cameras are included. There are of course solutions to these concerns though.

It is probably better that some devices (such as pacemakers) are simply never designed to have Internet connectivity to begin with. Thermostats and refrigerators are the type of devices which clearly don’t require Internet connectivity to fulfill their intended purpose. Letting them be connected to the Internet may be convenient, but it may very well not be worth the increased potential of compromising other devices and being compromised themselves, leading to substantial costs in unintended heating or spoiled food.

For the devices that are for whatever reason connected to the Internet, it’s better if there could be multiple networks with strong security in a home or building if possible. That way, if an IoT device is compromised on one network, devices on another network have another barrier of protection against being compromised.

This relates to a concept in security known as security by compartmentalization. Since all of today’s software contains flaws — vulnerabilities that can be exploited — the approach of compartmentalization seeks to limit damage before it can spread too far.

In terms of optimization, some things are worthwhile to have connected. Different machines or robots should be communicating with each other on a task such as how many raw materials are needed. This will save humans the need to say this, allowing them to focus on more productive tasks than those that merely report details.

As cooperation can be powerful among humans, so too can it be among machines and other devices. It’s going to require strong security practices such as implementing compartmentalization, having standards on security updates, and using better encryption schemes for software, but it can be done, and it should be done. Since technology has no moral imperative, what humans do with technology will likely either create dystopias or utopias. It’s a question of whether the Internet of Things will lead primarily to chaos or to widespread benefits.

Doing Math With Better Posture Improves Performance, Study Finds

The research has implications for other areas of performance too.

If you’ve ever felt like a deer in the headlights before taking a math test or speaking before a large group of people, you could benefit from a simple change in posture. As part of a new study by researchers at San Francisco State University, 125 college students were tested to see how well they could perform simple math — subtracting 7 from 843 sequentially for 15 seconds — while either slumped over or sitting up straight with shoulders back and relaxed. Fifty-six percent of the students reported finding it easier to perform the math in the upright position.

“For people who are anxious about math, posture makes a giant difference,” said Professor of Health Education Erik Peper. “The slumped-over position shuts them down and their brains do not work as well. They cannot think as clearly.” Before the study began, students filled out an anonymous questionnaire asking them to rate their anxiety levels while taking exams and performing math; they also described any physical symptoms of stress they experienced during test taking.

According to co-author Associate Professor of Health Education Richard Harvey, slumping over is a defensive posture that can trigger old negative memories in the body and brain. While the students without math anxiety did not report as great a benefit from better posture, they did find that doing math while slumped over was somewhat more difficult.

Peper and Harvey say these findings about body position can help people prepare for many different types of performance under stress, not just math tests. Athletes, musicians and public speakers can all benefit from better posture prior to and during their performance. “You have a choice,” said Peper. “It’s about using an empowered position to optimize your focus.”

That empowerment could be particularly helpful to students facing the challenge called “stereotype threat,” said Lauren Mason, one of the paper’s authors and a recent SF State graduate. A first-generation college student, Mason can identify with such students, who experience fear and insecurity because of a belief by others — which can become internalized — that they won’t do as well at math. Mason said she has benefitted personally from using a more empowered posture before taking difficult tests, including math. She believes that adopting a more confident posture could help other first-generation students as well as women entering science and math, who often battle stereotype threat, too.

“I always felt insecure about my math abilities even though I excelled at other subjects,” said Mason, who helped design the experiment in the study. “You build a relationship with [math] so early — as early as elementary school. You can carry that negative self-talk throughout your life, impacting your perception of yourself.”

Mason said the study results demonstrate a simple way to improve many aspects of life, especially when stress is involved: “The way we carry ourselves and interact in space influences not only how others perceive us but also how we perceive ourselves.”

AI System that Develops Drugs Developed

In a more sensible world, many more resources would be immediately put into this development to (benevolently) accelerate research into medicine. We would have more money for that if we didn’t allow pharmaceutical companies to charge ridiculous prices and then spend woefully inadequate amounts of their revenue on actual research.

An artificial-intelligence approach created at the University of North Carolina at Chapel Hill Eshelman School of Pharmacy can teach itself to design new drug molecules from scratch and has the potential to dramatically accelerate the design of new drug candidates.

The system is called Reinforcement Learning for Structural Evolution, known as ReLeaSE, and is an algorithm and computer program that comprises two neural networks which can be thought of as a teacher and a student. The teacher knows the syntax and linguistic rules behind the vocabulary of chemical structures for about 1.7 million known biologically active molecules. By working with the teacher, the student learns over time and becomes better at proposing molecules that are likely to be useful as new medicines.

Alexander Tropsha, Olexandr Isayev and Mariya Popova, all of the UNC Eshelman School of Pharmacy, are the creators of ReLeaSE. The University has applied for a patent for the technology, and the team published a proof-of-concept study in the journal Science Advances last week.

“If we compare this process to learning a language, then after the student learns the molecular alphabet and the rules of the language, they can create new ‘words,’ or molecules,” said Tropsha. “If the new molecule is realistic and has the desired effect, the teacher approves. If not, the teacher disapproves, forcing the student to avoid bad molecules and create good ones.”

ReLeaSE is a powerful innovation to virtual screening, the computational method widely used by the pharmaceutical industry to identify viable drug candidates. Virtual screening allows scientists to evaluate existing large chemical libraries, but the method only works for known chemicals. ReLeASE has the unique ability to create and evaluate new molecules.

“A scientist using virtual screening is like a customer ordering in a restaurant. What can be ordered is usually limited by the menu,” said Isayev. “We want to give scientists a grocery store and a personal chef who can create any dish they want.”

The team has used ReLeaSE to generate molecules with properties that they specified, such as desired bioactivity and safety profiles. The team used the ReLeaSE method to design molecules with customized physical properties, such as melting point and solubility in water, and to design new compounds with inhibitory activity against an enzyme that is associated with leukemia.

“The ability of the algorithm to design new, and therefore immediately patentable, chemical entities with specific biological activities and optimal safety profiles should be highly attractive to an industry that is constantly searching for new approaches to shorten the time it takes to bring a new drug candidate to clinical trials,” said Tropsha.

At least one of the creators of the AI system seems to have the wrong view of drug patents. Patents on “chemical entities” are definitely not what we need more of.

The U.S. spent $450 billion on prescription drugs in 2017, an amount that could have been about $380 billion less if there were no drug patent monopolies. With that $450 billion, the pharmaceutical industry spent around $70 billion in research and development — less money than they spent on stock buybacks that reward shareholders (and most people aren’t significant shareholders).

It would be sensible to get rid of drug patent monopolies that allow for ridiculous prices, and then simply have the government pay for the $70 billion in research directly. The difference would amount to a savings worth thousands of dollars per family, and it would mean better pharmaceutical research too.

Negative Energy Pricing Becoming More Common as Clean Energy Outdoes Fossil Fuels

Imagine living in a world where one of the most significant threats in the decades ahead is for the most part not being properly addressed, and is in many ways being exacerbated. The threat is climate change, and for one thing, it’s being exacerbated by having massive fossil fuel subsidies instead of massive clean energy subsidies. This is of course despite clean energy already regularly outcompeting fossil fuels.

Bright and breezy days are becoming a deeper nightmare for utilities struggling to earn a return on traditional power plants.

With wind and solar farms sprouting up in more areas — and their power getting priority to feed into the grid in many places — the amount of electricity being generated is outstripping demand during certain hours of the day.

The result: power prices are slipping to zero or even below more often in more jurisdictions.

[…]

Periods with negative prices occur when there is more supply than demand, typically during a mid-day sun burst or early morning wind gust when demand is already low. A negative price is essentially a market signal telling utilities to shut down certain power plants. It doesn’t result in anyone getting a refund on bills — or in electric meters running backward.

Instead, it often prompts owners of traditional coal and gas plants to shut down production for a period even though many of the facilities aren’t designed to switch on and off quickly. It’s left the utilities complaining that they can’t earn the returns they expected for their investment in generation capacity.

Facebook Seeking to Exploit Consumer Banking Data

Major corporations are interested primarily in profits, not helping human beings. Since data is clearly one of the most valuable resources in the world today, major corporations trying to obtain consumer banking data represents the corporations trying to further engage in data mining and exploitation.

Apparently not satisfied with access to its users’ call history, text messaging data, and online conversations, Facebook has reportedly asked major Wall Street firms like JPMorgan Chase and Wells Fargo to hand over their customers’ sensitive financial data as part of the social media giant’s ongoing attempt to become “a platform where people buy and sell goods and services.”

And according to the Wall Street Journal—which first reported on Facebook’s plans on Monday—the social media behemoth isn’t the only tech company that wants access to Americans’ financial data. Google and Amazon have also “asked banks to share data if they join with them, in order to provide basic banking services on applications such as Google Assistant and Alexa,” the Journal pointed out, citing anonymous sources familiar with the companies’ ambitions.

Over the past year, Facebook has reached out to some of America’s largest banks to request “detailed financial information about their customers, including card transactions and checking account balances, as part of an effort to offer new services to users,” the Journal notes. “Facebook has told banks that the additional customer information could be used to offer services that might entice users to spend more time on Messenger.”

In response to the Journal‘s reporting, critics of corporate power used the word “dystopian” to describe the push by Facebook, Google, and Amazon for ever-greater access to users’ personal information in a bid to boost profits.

[…]

While Facebook insisted in response to the Journal‘s story that it doesn’t want to use any of this data for advertising purposes or share it with third parties, many pointed out that there is no reason to trust Facebook’s expressed commitment to user privacy, particularly in the wake of the Cambridge Analytica scandal and other abuses.

Democratic Socialism in the Era of Ocasio-Cortez and Sen. Sanders

Democratic socialism has been more in the news lately since the most popular American politician — Senator Bernie Sanders — and a rising star in the progressive movement, Alexandria Ocasio-Cortez (who won an upset victory in a primary vs. an incumbent New York House politician) both profess to be democratic socialists. With this being the case, it is worth examining what the ideology represents and how it’s being used.

Democratic socialism (at least by what it should mean by definition) at its core means the democratic control over the means of production. This would mean that instead of institutions such as factories, banks, and media companies being controlled primarily by a small group of (often wealthy) people pretty much functioning outside of democratic controls, there would be much more stakes of shared ownership among the public. Under such an ideology, many more people would, for example, have the authority to join together and hire and fire their managers instead of the other way around.

When Ocasio-Cortez and Sanders mention democratic socialism though, they don’t usually say much about democratizing the distribution and organization of production. In truth, what they’re usually referring to is what’s called social democracy — letting the means of production still be controlled pretty undemocratically in capitalistic fashion, but at least in a way that also includes significant government intervention benefits for the general public. This includes a national healthcare system (which all OECD countries besides the U.S. and Mexico have), decently high taxes on rich people, educational costs being covered by the government, and a variety of other social programs such as paid maternity leave.

In the United States, subscribing to social democracy is often regarded as being pretty far left on the political spectrum. This is really just a reflection of the immense rightward shift of U.S. politics since the 1970s though. For one example, Republican president Dwight D. Eisenhower of the 1950s was a strong supporter of both unions and the New Deal social welfare programs implemented under president Franklin Roosevelt. Eisenhower said that those who didn’t accept the New Deal programs didn’t belong in the political system, but not accepting those programs has now become the norm among Republicans and among many Democrats as well. That Eisenhower would today be regarded as clearly on the left side of the political spectrum truly says a lot about American political discourse.

In terms of socialism, older Americans tend to associate socialism with the Soviet Union. The problem with that is that the Soviet Union practiced state socialism — there wasn’t any democratic distribution of resources there. The Soviet Union was in large part a dungeon for a lot of its people that provided some minimum subsistence benefits to let many of them survive.

And it should be noted that the achievements of the Soviet Union were when it was able to use the power of the state to direct people and resources to useful developmental ends, such as its space program. In the 20th century, it grew quickly from a largely poor and illiterate society that had been invaded multiple times to a world superpower for a few decades, and whatever criticisms of the USSR, there is something to be learned there. It’s a similar parallel to why China has grown and continues to grow as fast as it does — a fairly efficient use of resources (evidently quite powerful), even if the conditions that’s done under happen to be cruel.

The Soviet Union replaced the employers that hold so much power in capitalism with state officials. This didn’t change the fundamental dynamic of workers being quite disempowered, and in many ways made the situation in the Soviet Union worse than it would have been under capitalism. Democratic socialism seeks to absolve the everlasting struggle between the employer and employee, those who own and those who don’t, and in truth the ideology has never been tried much at scale. There are reasons to think that it would be a better way to organize society, such as research showing that today’s employees become more productive when given more autonomy, but there isn’t enough data to know for sure. The experiment of having a large worker cooperative sector of the economy could be run, just like the massive experiments of tax cuts for the rich have been run multiple times, although that’s obviously rather dangerous — it may actually provide a significant benefit to the lives of average working people.

It should also be noted how puzzled some people in the media are by young Americans’ embrace of socialism over capitalism. A now well-known Harvard study that was conducted in 2016 — and was redone once since the ones commissioning it were stunned at the results — showed that 51 percent of young Americans rejected capitalism and 33 percent preferred socialism.

This isn’t really an acceptance of socialism — it’s more of a rejection of capitalism. Young people in general have a vague awareness that the system isn’t working real well for them. Letting the money speak, real wages (wages with respect to inflation) in the United States have been almost entirely stagnant for decades. The only times most workers have seen real wage gains since the late 1970s have been in the later 1990s and over some of the last several years. Both of these periods had tight labor markets from the Fed allowing interest rates to remain low. In the 1990s it was because Alan Greenspan was a somewhat atypical economist and, for some reason, bucked the mainstream of his profession by allowing interest rates to remain low — in other words, something akin to dumb luck. In recent years it was because the Great Recession forced the Fed to drop interest rates to zero and near zero in order to provide a stimulus to the economy (in other words, a massive disaster had to happen).

Additionally, it’s probably pretty irrational to regard capitalism as the only or most viable economic system. It’s just an economic system, but those who reject it are often deemed heretics. In America there are plenty of debates, but for a few generations at least, the debate over the fundamental distribution of resources has been to a significant degree left out.

One view on that though is that this debate between capitalism and a different economic system isn’t really necessary or prudent, and that it would be better to have the debate over how markets are structured and to advocate for structuring them in ways that don’t redistribute income upward. Good Keynesian economists that primarily represent the working class may tend to advocate this view. That may admittedly be a better way to help the modern working class, but will there nonetheless be a massive cost to future generations if capitalism is maintained?

Even Minor Dehydration Can Make Thinking More Difficult

If climate change leads to increased temperatures throughout the world, people will sweat off water faster, meaning that they will become dehydrated more quickly. This has clear implications for possibly reducing the average level of decision making among humans.

If you’re finding it hard to get your thoughts straight, dehydration could be to blame. An analysis of previous research has found a link between dehydration and poor performance in tasks that need serious focus or advanced mental processing.

While we know that staying hydrated is good for us for all kinds of reasons, this new meta-study was designed to take a closer look at exactly which brain processes might be affected and at what level of dehydration.

It turns out that at just a 2 percent level of body mass loss due to dehydration – so losing about a litre of water through sweat – the mental imbalance starts. That underlines how crucial it is for us to keep up our water intake, and how damaging it might be to the mental agility we all rely on if we don’t.

“We find that when people are mildly dehydrated they really don’t do as well on tasks that require complex processing or on tasks that require a lot of their attention,” lead researcher Mindy Millard-Stafford, from the Georgia Institute of Technology, told Allison Aubrey at NPR.

Millard-Stafford and her colleague Matthew Wittbrodt looked at 33 previous studies linking dehydration with mental performance. In total, the studies covered a total of 413 individuals experiencing between 1 percent and 6 percent of body mass loss through dehydration.

That 2 percent point seems to be the tipping point when it comes to staying mentally sharp. According to the experts, it would maybe take an hour’s hike to get to that level.

What’s more, it’s a level of dehydration that we might not actually notice through triggers like increased thirst: so mental performance could decline even when we don’t feel like we need to take on any water.

The analysis backs up previous research suggesting that dehydration impairs some mental processes more than others, with attention, executive function, and motor coordination particularly hard hit. Lower-level tasks like reaction time aren’t as badly affected, the meta-study shows.

While it’s different for every individual, experts recommend that women get up to 2.7 litres or 95 fluid ounces (11.5 cups) of water every day, and men up to 3.7 litres or 130 fluid ounces (15.5 cups).

The body as a whole is 60 percent water, which it leverages for jobs like transporting nutrients around the body and lubricating our eyeballs.

When there isn’t enough water available – it’s regularly lost through sweating and urination – these vital functions start to break down. We become thirsty, start to feel nauseous, and become more likely to feel exhausted.