Pengju Li, a researcher on the study, holds a prototype pacemaker that’s only 1 micrometer thick, and operated by light pulses
Scientists at the University of Chicago have developed a new pacemaker that’s thinner than a human hair, wireless and operated entirely by light from an optic fiber. The non-invasive device could help regulate heart activity or even stimulate neurons in a set pattern to treat symptoms of conditions like Parkinson’s.
The heart pumps thanks to a series of very carefully timed electrical signals, but if those signals fall out of time, they can lead to all sorts of issues, such as strokes, heart attacks or even a fatal failure of the organ. Pacemakers monitor and correct these abnormal rhythms, but they require invasive surgeries and bring their own risks.
The new device is much less invasive – it’s a thin film just one micrometer thick, which is about 100 times thinner than a human hair, or a recent similar device made of graphene which was also 100 micrometers thick. It tips the scales at just one 50th of a gram, making it 250 times lighter than a regular pacemaker. And rather than needing a battery, it’s powered by light.
Obviously light doesn’t usually reach the heart (unless something is terribly wrong), so an extremely narrow optic fiber is inserted alongside it. The fiber lights up in a specific pattern, which triggers the thin film to produce an electric current. The film is made of two layers of P-type silicon – the top layer is dotted with nano-scale holes that confine the electricity, allowing the device to stimulate very specific parts of the heart on demand, producing the desired rhythm.
The team tested the device in human heart tissue grown in the lab, then in isolated rat hearts, then moving up to living mice and rats, and finally to living pigs. In all cases, the technique worked to stimulate the heart’s rhythm as needed, requiring only endoscopic surgery rather than opening up the chest cavity.
In its current form, this thin pacemaker is designed to be temporary, dissolving into a nontoxic compound called silicic acid, which negates the need for another round of surgery to remove it. But the team says that future versions could be adapted to last different time frames.
The researchers also say that the device could be used to stimulate nerves on demand, in specific patterns. This could be used to treat the symptoms of conditions like Parkinson’s or chronic pain.
Its creators hope the technology will help people meaningfully connect with the external world.
A hand prosthesis outfitted with MindTouch for integrated thermal feedback.
KEY TAKEAWAYS
The earliest known prosthetics date back to ancient Egypt. One, called the “Cairo toe,” shows signs that it wasn’t simply cosmetic. Even 3,000 years ago, the wood-and-leather digit was designed for flexibility, suggesting it provided function alongside form.
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Since then, people have worked hard to find ingenious means of improving the lives of people with amputations. Starting as early as the 15th century, engineers began incorporating cables, gears, and springs into prosthetics to give people the — albeit limited — ability to grasp objects and bend joints. Prosthetics were built to perform specific tasks, such as holding shields or playing the piano. And they became more comfortable with the discovery materials like rubber, plastics, and lightweight metals.
A prosthetic toe from ancient Egypt now housed in the Egyptian Museum, Cairo. The big toe is carved from wood and attached by a leather wrap.
However, until recently, one advance has been missing from this history: touch. Figuring out how to elicit feeling through a prosthetic is important because limbs and appendages aren’t simply mechanical tools. A person’s sense of touch allows them to embody experiences, and absent that, there remains a meaningful disconnect from the external world.
“Temperature is one of the last frontiers to restoring sensation to robotic hands. For the first time, we’re really close to restoring the full palette of sensations to amputees,” Silvestro Micera, the Bertarelli Foundation chair in translational neuroengineering at the Swiss Federal Institute of Technology Lausanne (EPFL), says.
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Micera is part of a research team developing a device capable of doing just that. Their latest study, published last month in the journal Med, shows that the device can not only help a person distinguish between temperatures but that it can be paired with already existing prosthetics.
Feeling phantom heat
They call their tech “MindTouch,” and a previous study explains how it taps into “phantom thermal sensations.”
Phantom sensations (aka phantom limb syndrome) are the feeling that a missing limb is still there. For instance, if a person has had a hand amputated, they may sometimes feel the absent appendage moving or even being touched. Around 60-80% of amputees report phantom sensations, and for some, they can even be painful.
But MindTouch uses phantom sensations to its advantage.
The procedure starts with the researchers mapping a person’s residual limb to discover areas that reliably elicit phantom sensations when experiencing hot or cold. Over several mapping sessions, they identify the place that most consistently elicits phantom sensations.
They then retrofit a user’s prosthetic with a device called a “thermode.” The thermode rests against the user’s skin at that consistent point, sending temperature signals to the nerves of the residual limb. The temperature signals are retrieved by sensors placed on the fingertips of the prosthetic.
As one participant in the study explained, “The most impressive for me was when the experimenter placed the sensor on his own body. […] I could feel the warmth of another person with my phantom hand. It [was] having a connection with someone.”
For the current study, the researchers enlisted the help of a 57-year-old man who had a transradial amputation. The participant reported having mild to no phantom limb pain. Over 130 days, the researchers performed the thermal mapping before augmenting the participant’s prosthetic arm with MindTouch. They then performed a series of tests to determine if he could pick up on temperature differences.
The study participant’s prosthetic arm outfitted with MindTouch. Using the integrated thermal feedback, he is sorting warm and cold stainless steel cubes with a high accuracy.
During the first test, the participant was asked to close his prosthetic hand around three indistinguishable brown bottles, filled with either hot, cold, or lukewarm water.
The second test asked the participant to identify copper, glass, or plastic slabs while blindfolded. Another blindfold test had him guessing whether he was touching a real human hand or an artificial silicone one. The fourth and final test had him sort identical stainless steel cubes that were either hot or cold.
“Our goal is to develop a multimodal system that integrates touch, proprioception, and temperature sensations,” Solaiman Shokur, study author and neuroengineer at EPFL, says. “With that type of system, people will be able to tell you ‘this is soft and hot,’ or ‘this is hard and cold.’”
Getting back in touch (with touch)
How did he do? In all of the tasks, the participant scored better than chance.
He aced the bottle test with MindTouch turned on, scoring 100% accuracy. In the blindfolded tests, which looked toward more subtle temperature differences, he correctly discerned between the human and artificial hands 80% of the time and correctly differentiated between the various materials 67% of the time, and could easily distinguish between plastic and copper. Finally, over various sessions of block sorting, he correctly placed 114 out of 153 blocks for an accuracy of 64%.
In all of these tests, when MindTouch was turned off, his accuracy dropped to chance level. In the case of the bottle sorting test, it was only 33%.
We think having the ability to sense temperature will improve amputees’ embodiment — the feeling that “this hand is mine.”Solaiman Shokur
Interestingly, for two of the tests, bottle and materia sorting, he performed just as well with MindTouch as with his intact hand. The test where the prosthetic fell short by comparison was the handshake test; the researchers believe that other tactile sensations, such as skin texture, may have made the difference.
All told, the thermal sensations remained stable over 400 days, and because the device is noninvasive, no adverse effects were recorded.
“Adding temperature information makes the touch more human-like,” says senior author Shokur added. “We think having the ability to sense temperature will improve amputees’ embodiment — the feeling that ‘this hand is mine.’”
Moving forward, the team hopes to expand their studies to a larger cohort and determine how out-of-the-lab factors like air temperature and humidity affect MindTouch. They also note several challenges that will need to be overcome. Chief among these is devising a way to integrate multiple thermodes to evoke larger portions of someone’s phantom hand. They will also need to find a way to miniaturize the battery and controller unit to be more user-friendly.
“But these challenges are worth the effort,” the authors write, “as the long-term use of the thermal prosthetic hand could open completely new perspectives for prosthetic users. […] For the first time, we can envision the possibility of restoring a multimodal palette of natural sensations.”
Scientists in the UK have even identified four cases of “chronic déjà vu.”
A young woman experiencing déjà vu.
Have you ever experienced déjà vu? If so, you are among the 60-70% of the population who has. The majority of those who report déjà vu are between the ages 15 and 25. I’m a complete rationalist who believes that every phenomenon, no matter how strange or supernatural it appears, has a scientific reason behind it. Even so, I’ve met several people and walked into a few situations where, though I had never been there before or met the person before, I suddenly felt awash in a bizarre familiarity. This transcendental sensation can shake beliefs such as mine right to their very core.
But I wasn’t ready to denounce science yet. And I’m glad. Because it turns out, there is a rational explanation. Though some radical notions have in the past been connected to this strange feeling, such as déjà vu being a momentarily aligning with a past life or another you in a parallel universe, or as my editor suggests—a glitch in the matrix, scientists now believe it has a neurological basis.
Unfortunately, the feeling is here one minute and gone the next, making it difficult to study. Even so, there are quite a few theories on what causes it. One traditional hypothesis, posited by psychiatrists, is mismatched brain signals. For a second it feels as though we are transported to a moment in the past and we mistake it for the present. This may be why it’s been associated with the idea of reincarnation.
0 seconds of 5 minutes, 52 secondsVolume 90%
Another theory is that déjà vu is our brain trying to piece together a situation on limited information. A third states that it is a misfiring in the parts of the brain that recall memory and decipher sensory input. Sensory information, rather than taking the proper channels, leaks out of the short-term memory and into the long-term one. In this way, current experiences seem to be connected to the past. Some studies even suggest that familiar geometric shapes give us a sense of knowing something about a place that is, in reality, totally unfamiliar to us.
Instead of a glitch in the matrix, déjà vu may just be a glitch in our memory.
Since we are completely aware of everything that’s going on when we experience déjà vu, this suggests that every part of the brain need not participate for the sensation to take place. Psychologist Anne M. Cleary at Colorado State University, in a study in 2008, found that déjà vu followed patterns we associate with memory, specifically recognition memory. This is the kind that gets us to understand that we are confronting something that we’ve seen or experienced before. If you’ve ever recognized a landmark, a friend from across the room, or a song on the stereo, you’ve experienced recognition memory.
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Familiarity-based recognition is associated with it. Here, we have that feeling of familiarity, but we can’t quite place where we’ve seen this person, place, or thing. For instance, you recognize someone across the street, but can’t remember their name or where you know them from. Prof. Cleary conducted several studies which found that déjà vu is a form of familiarity-based recognition. Her work suggests that our memory stores items in fragments. When there is a certain overlap between old and new experiences, we have strong feelings about the connection, which we interpret as déjà vu.
Recent studies looking at epileptic patients made impressive breakthroughs in our understanding of the phenomenon. Epileptics with certain intractable conditions require electrodes to be placed inside their brains in order to locate the source of their seizures. During this procedure, some neurologists have had patients experience déjà vu. They soon discovered that the phenomenon takes place in the medial temporal lobe, which is responsible for memory. The electrodes are usually placed within the rhinal cortex—the most important piece of which is the hippocampus, the structure responsible for long-term memory formation. French scientists have found that firing current into this cortex can trigger an episode of déjà vu.
Location of the amygdala and the hippocampus. By OpenStax College [CC BY 3.0], Wikimedia Commons.
The French study, published in the journal Clinical Neurophysiology, measured EEG wave patterns from patients with epilepsy who experienced déjà vu through electrical stimulation. The areas of the brain they examined included the amygdala, which is responsible for emotion and the hippocampus. Researchers found that electrical patterns, emanating from rhinal cortices and the amygdala or the hippocampus, caused déjà vu to occur. These neuroscientists believe that some sort of electrical phenomenon in the medial temporal lobe activates the memory in such a way that it causes déjà vu to occur.
Stranger still, scientists in the UK have actually found patients who experience “chronic déjà vu.” In this case, experts identified four senior citizens who encounter the feeling on a consistent basis. What is the impact of such a phenomenon? It made them feel as if they were clairvoyant. All four refused to go to the doctor, believing they already knew what the physician would say, and avoided watching the news, thinking they already knew the outcome. That’s because each time they took part in either activity that was the result they came to.
Each individual experienced some type of problem with the temporal lobe of their brain. The circuits in that area were in a sense stuck in the “on” position. It just goes to show that when we don’t know the reason for a phenomenon or sensation, our mind assigns a meaning to it. But that isn’t necessarily the correct one. And even though knowing the neurological basis of déjà vu may evaporate the supernatural awe surrounding it, understanding the phenomenon better puts a scientific mind, like mine, at ease.
A recent study suggests that moderate exposure to solar radiation during autumn and spring may improve ovarian reserve in women ages 30–40.
Results from a recent study suggest that moderate exposure to solar radiation during autumn and spring may help improve ovarian reserve in women ages 30–40.
It’s too soon to determine the effects of solar radiation on fertility outcomes, particularly in younger age groups.
Research is ongoing about which factors affect female fertility and how women can modify these factors.
Many people face fertility challenges, particularly those who are over 35.
Researchers are exploring various potential causes of infertility, such as environmental factors, and whether modifying these factors could have any affect on fertility outcomes.
A recent study published in Steroids examined how exposure to solar radiation influences female fertility. Researchers examined levels of a specific hormone called anti-Müllerian hormone (AMH) and how levels of this hormone varied during different times of the year.
The results were significant for women over 30 who experienced higher levels of AMH in the spring and autumn when there were moderate levels of solar radiation intensity.
However, researchers did not observe this effect in women under 30, indicating that solar radiation may affect female fertility more with age. More research is required to understand these factors and the potential clinical implications.
Researchers looked at how sun exposure influenced fertility among women of younger and older maternal age. This study was conducted in Israel and included 2,235 women mainly between 20 and 40 years old.
Researchers wanted to better understand the relationship between solar radiation exposure and anti-Müllerian hormone (AMH), an indicator of female fertility.
“When evaluating the fertility status of a patient, often, an anti mullerian hormone level is obtained. This level correlates to ovarian reserve. Studies have revealed that AMH declines with age, and therefore also does fertility,” non-study author Dr. Kelli V. Burroughs, a national media women’s health medical expert and department chair of OB-GYN at Memorial Hermann Sugar Land in Texas, explained to Medical News Today.
However, researchers of the current study note that AMH doesn’t necessarily reflect the quality of oocytes.
The study authors looked at participant data for 4 years. Researchers measured solar radiation in the central district of Israel using data from the Israeli Meteorological Service website.
Researchers found that AMH levels declined with age, so they divided participants into two groups: aged 20-29 years and 30-40 years. For women in the 20–29-year category, researchers did not find an association between AMH levels and the seasons or solar radiation intensity.
However, the results differed for women in the 30–40 year group. Researchers found that AMH levels increased for these women in the spring and autumn when there were moderate solar radiation intensity levels compared to the winter months when there were low solar radiation intensity levels.
The levels of AMH during months of moderate solar radiation exposure were overall higher than months that had high or low-intensity solar radiation levels.
They also found that participants in the 30–40-year group who had AMH levels collected during the summer months had much higher AMH levels than participants who had AMH levels collected during the winter months.
Researchers further divided participants into 30–35-year and 36-40-year groups. In the 30–35-year group, they did not find a significant correlation between solar radiation intensity or season and AMH levels. In the 36–40 group, they discovered that AMH levels were higher in the months of moderate solar intensity and higher in the summer compared to winter.
The results indicate that exposure to moderate solar radiation may be helpful for women in their 30s who are trying to get pregnant.
Dr. Burroughs noted the following:
“This study is interesting because it suggests for women between ages 30-40 there is a possible seasonal influence on the AMH driven by the amount of sunlight or UV exposure. The mechanism behind the correlation of AMH and seasonal UV light exposure is unknown, but the study revealed higher levels of AMH with moderate UV exposure during spring and fall. It was also noted that low and high levels of UV exposure had the opposite effect on AMH levels.”
Fertility is complex and affected by many components. Sometimes, it’s possible to modify certain factorsTrusted Source that may contribute to infertility.
For example, both obesity and being underweight can increase the risk of infertility. Smoking or heavy drinking can decrease fertility. Certain health conditionsTrusted Source can also impact female fertility, such as:
Non-study author Dr. Kecia Gaither, MPH, double board-certified OB-GYN and maternal-fetal medicine specialist and director of Perinatal Services/Maternal Fetal Medicine at NYC Health in New York, told MNT:
“There are many factors which impact fertility — drugs, stress, female factors (endometriosis, fibroids, polyps, hormonal imbalances, PCOS etc) [and] male factors (i.e., low sperm counts). It’s important to note the environmental aspect — (i.e., plain sunlight exposure) as a factor correlating with positive reproductive health [or] outcomes.”
One non-modifiable factor that affects female fertility is advanced maternal age as the chances of successful conception begin to decline after 35.
Dr. Burroughs noted the following:
“More women than ever are delaying childbirth until their 30s and 40s for a variety of reasons including education, employment obligations, career-goals and increase[d] access to contraception. The result of delayed childbearing until the 3rd or 4th decade in life can impact fertility, because as a woman ages the ovarian reserve or number of eggs starts to decline. After the age of 35, a woman is considered advanced maternal age (AMA). This terminology reflects the correlation between age and declining fertility status.”
This study does have limitations. First, it doesn’t establish any causal relationship between the observed components.
Researchers also acknowledge that the lack of any significant association between AMH and seasons and participants between 20–29 years could be because of the difference in sample size between this group and the older group.
Researchers also acknowledge that they did not analyze luteinizing hormone (LH) and follicular stimulating hormone (FSH) hormone levels in women aged 26–30, and this could have impacted their findings in this area.
Researchers also note the possibility of confounding related to things like skin tone and cultural distinctions. Other factors like lifestyle and personal choices of participants could have also impacted the results.
The research also focused on one area of the world, so the results could be different if conducted in other countries. Researchers did not take into account the origin of participants in their analysis. Finally, researchers did not have access to certain clinical information, like reproductive history.
As research continues, study authors note that the potential benefits should be balanced with the possible risks of sun exposure, such as cancer or skin damage.
Here’s how to structure your days, so that you’re setting yourself up for a long and healthy life.
Every day we’re inundated with the “right” things to do to live a longer life. Drink eight glasses of water a day, they say. Go to the pharmacy for an off-label prescription, advise others. And others task us with the impossible—yet promising—task to just keep a positive mindset.
Today, the average life expectancy in Britain is 81, and in 2022 there were over 15,000 people over the age of 100 living in England in Wales. But in the Blue Zones, or regions of the world where people live exceptionally long lives, individuals are ten times more likely to live to 100. These places—specifically the Barbagia region of Sardinia, Italy, Okinawa, Japan, Nicoya Peninsula, Costa Rica; and Icaria, Greece—are packed with centenarians.
It was only a matter of time until medical researchers, demographers, epidemiologists, and anthropologists dug in to find out the common denominators among these places. Thus, emerges the Blue Zones “Power Nine”—or nine things that the five places who have the highest proportions of people who reach age 100—have in common. National Geographic’s Dan Buettner, published these findings in his book, The Blue Zones: Lessons for Living Longer From the People Who’ve Lived the Longest. We tapped our own longevity experts to weigh in on each of the nine pillars.
1. Move naturally
Studies show that sedentary behaviour like sitting for 13 hours a day or walking less than 4,000 steps per day can reduce the metabolic benefits of acute exercise, while occasional activity could help reduce post-meal insulin levels. Researchers even found that “soleus push-ups” (that’s calf raises for the majority of us) done in a sitting position have been shown to fuel metabolism for hours. In other words: You don’t need to set aside 90 minutes every day to exercise day after day. Exercise snacks, or small bouts of movement incorporated throughout the day, are proven to be just as effective as larger planned-ut workouts—and much more accessible to most.
So, where does someone begin? Dr. Kien Vuu, founder of Vuu MD Performance and Longevity, author of Thrive State, says it starts by thinking of your work day differently. Have a bike? Opt for walking or biking for short distances, including to the office if that’s an option for your commute. Once you’re at your desk, try leg lifts or seated stretches, take the stairs to grab coffee, or opt for walking meetings if you’re chatting with someone who’s also in-office. Just a few minutes of activity breaking up sedentary behaviour can reap many benefits.
2. Say yes to happy hour
By now, most everyone has indulged in a non-alcoholic beverage, whether or not you’re on Team Dry January/Sober October. Although there’s loads of research praising the benefits of ditching alcohol altogether, a glass of wine is praised in Blue Zones. Not because of the wine’s health benefits, per say, but more so because of the socialization that comes hand-in-hand with imbibing now and then. “In longevity cultures, moderate alcohol consumption often occurs in a social context, emphasizing the role of community and celebration,” says Dr. Vuu. “The key might lie more in the positive social interactions and less in the alcohol itself. Positive relationships contribute to mental and emotional well-being.”
3. Take time to downshift
We’ve all heard it before: Stress is no good for us. Still, it’s often unavoidable. “When you notice your body tensing or your emotions rising, take a deep breath, hold for a few seconds, and slowly breathe out through your nose,” says Dr. Michelle Loy, an integrative medicine specialist at NewYork-Presbyterian/Weill Cornell Medical Center and assistant professor of pediatrics in clinical medicine at Weill Cornell Medicine. “The more you practice this, the better it gets. It can be done anywhere, anytime, and doesn’t interact with any medications or supplements.”
Not sure where to start? Begin before bedtime, making a couple extra minutes before you fall asleep to practice. Then, bring it into other areas of your day.
4. Give your diet a plant slant
Rich Roll. Chris Paul. Justin Fields. Kevin Hart. We’ve covered loads of guys who stick to a mostly plant-based diet (and exhausted the benefits of a plant-based diet, too). Blue Zone researchers agree, recommending that individuals seek out plant-based sources of protein, like beans, including black, soy, fava, and lentils, over meat. And when you’re in the mood for an animal-based option, opt for 3- to 4-ounce serving of pork.
5. Find your crew
If there’s one thing many learned during the last few years when it was at times stripped away from our day-to-day, there’s extreme power within connection and friendship. Those that live the longest identify close friends, and commit to those relationships for life. “Love and positive social interactions have been shown to release oxytocin, known as the ‘love hormone,’ which plays a role in bonding and reducing stress levels,” says Dr. Vuu. “So, loving, supportive relationships can lead to long-term improvements in emotional state and physical health.”
6. Abide by the 80 per cent rule
Researchers found that the people in Blue Zones eat their smallest meal in the late afternoon or early evening—then don’t eat any more the rest of the day. This falls into what’s called the “80 per cent Rule,” which recommends people stop eating when their stomachs are 80 per cent full. If you’re not good at exercising this type of restraint. Dr. Loy has a tip: “When you are starting to feel full, put away part of your meal in a Tupperware—or ask for the server to pack it to go,” she says.
7. Put your loved ones first
Investing time in your family is something that not only pays off emotionally, but in terms of longevity as well. Successful centenarians keep aging parents (or grandparents) nearby, commit to a life partner, and if they have children, they make an effort to spend time with them.
8. Find a place you belong
Research shows that attending a faith-based service four times per month could add four to 14 years to your life expectancy. If religion isn’t your cup of tea, there’s always the opportunity to dive deep into your own personal wellness. Seek out a squad that makes you feel accepted and seen, whether that’s your local CrossFit gym or a weekly trivia ritual at the restaurant down the block.
9. Know your “why”
When you know why you wake up in the morning and have a purpose in your day-to-day life, research shows that you can add up to seven years to your life expectancy. The Japanese concept of Ikigai encourages individuals to find their personal calling or purpose, adds Dr. Loy, who recommends asking yourself four questions and finding where these answers intersect:
What do I love? (Passion)
What am I good at? (Profession)
What does the world need? (Mission)
What can I be compensated for? (Vocation)
“It may take some soul-searching, but it is worth taking the time to engage in this personal quest, as when you find your Ikigai, or several, it brings clarity to how you live your life,” she says.
Impaired brain energy metabolism has been observed in many neurodegenerative diseases, including Parkinson’s disease (PD) and multiple sclerosis (MS). In both diseases, mitochondrial dysfunction and energetic impairment can lead to neuronal dysfunction and death. CNM-Au8® is a suspension of faceted, clean-surfaced gold nanocrystals that catalytically improves energetic metabolism in CNS cells, supporting neuroprotection and remyelination as demonstrated in multiple independent preclinical models. The objective of the Phase 2 REPAIR-MS and REPAIR-PD clinical trials was to investigate the effects of CNM-Au8, administered orally once daily for twelve or more weeks, on brain phosphorous-containing energy metabolite levels in participants with diagnoses of relapsing MS or idiopathic PD, respectively.
Results
Brain metabolites were measured using 7-Tesla 31P-MRS in two disease cohorts, 11 participants with stable relapsing MS and 13 participants with PD (n = 24 evaluable post-baseline scans). Compared to pre-treatment baseline, the mean NAD+/NADH ratio in the brain, a measure of energetic capacity, was significantly increased by 10.4% after 12 + weeks of treatment with CNM-Au8 (0.584 units, SD: 1.3; p = 0.037, paired t-test) in prespecified analyses of the combined treatment cohorts. Each disease cohort concordantly demonstrated increases in the NAD+/NADH ratio but did not reach significance individually (p = 0.11 and p = 0.14, PD and MS cohorts, respectively). Significant treatment effects were also observed for secondary and exploratory imaging outcomes, including β-ATP and phosphorylation potential across both cohorts.
Conclusions
Our results demonstrate brain target engagement of CNM-Au8 as a direct modulator of brain energy metabolism, and support the further investigation of CNM-Au8 as a potential disease modifying drug for PD and MS.
Scientists are investigating whether an oral drug sprinkled with gold nanoparticles could one day treat neurodegenerative diseases like Parkinson’s and multiple sclerosis.
The experimental medicine, called CNM-Au8, has now shown success in boosting the brain’s metabolism in phase II clinical trials.
Research on the safety and efficacy of the daily drug is still ongoing, but the initial results have researchers hopeful. The medicine contains suspended nanoparticles of gold that can apparently pass the blood-brain barrier and improve energy supply to neurons, preventing their decline.
“We are cautiously optimistic that we will be able to prevent or even reverse some neurological disabilities with this strategy,” says neurologist Peter Sguigna from the University of Texas Southwestern.
Parkinson’s and multiple sclerosis (MS) are neurological diseases that feature signs of slow brain metabolism. This is thought to starve neurons of necessary energy and result in a build-up of harmful toxins and unstable molecules called free radicals that can damage cells.
The experimental drug, CNM-Au8, is designed to work like an energy stabilizer for the brain.
The choice of material might sound unnecessarily flashy, but crystals of gold nanoparticles are very different to the yellowish metal we’d turn into rings and necklaces. The tiny wine-red flecks can be cheaply synthesized and tweaked to rapidly enter cells or cross the blood-brain barrier to deliver medicine, making them ideal for use as pharmaceuticals.
The modifications that could be made to such drugs are seemingly limitless, and their potential to treat neurodegenerative disease is exciting, although current studies are still mostly confined to animals.
CNM-Au8 is among the first to make it to human clinical trials. The medicine is specifically engineered to provide the brain with a coenzyme critical to energy metabolism and the production of cellular fuel called adenosine triphosphate (ATP).
The coenzyme is one that can exist in two forms: oxidized (NAD+) and reduced (NADH). The ratio of these forms in the brain is essential to maintaining metabolic balance.
In patients with Parkinson’s and MS, NAD+/NADH ratios are unusually low and are indicative of the state of disease.
In recent clinical trials, however, when 13 patients with Parkinson’s and 11 patients with MS took CNM-Au8 every day for 12 or more weeks, their baseline NAD+/NADH ratio increased by an average of 10.4 percent.
That’s a relatively large treatment effect, given that some studies estimate the average person loses about 0.5 percent to their NAD+/NADH ratio per decade.
The improvement is hypothetically sufficient enough to reverse declines in neurodegenerative disease, not just stall them, the researchers say.
How the drug achieves this remains unknown, but preclinical studies on CNM-Au8 suggest that CNM-Au8 penetrates the blood-brain barrier and “triggers an increase in energy production in the form of ATP.”
In animal studies, CNM-Au8 also seems to counter some of the signs of MS, such as undoing damage to the sheaths that surround neurons and allow them to send messages more efficiently.
“To our knowledge,” the researchers at UT Southwestern write, “CNM-Au8 is the only suspension of gold nanocrystals with both exceptionally high catalytic activity and very low toxicity that is being developed as a disease-modifying agent for neurodegenerative disease.”
The potential benefits shown in phase II clinical trials have the team preparing for phase III.
An illustration of what the view might look like from the Kuiper Belt.
There may be a lot more than we thought to the belt of icy debris that circles the outer Solar System.
Data from the New Horizons probe as it sails serenely through the Kuiper Belt hints at unexpected levels of particles where dust ought to be thinning out, suggesting the donut-shaped field extends significantly farther from the Sun than previous estimates suggest.
It’s the most recent in a growing body of evidence that our understanding of the outer Solar System is lacking – but could help us better understand our planetary system, and others out there in the wider galaxy.
“New Horizons is making the first direct measurements of interplanetary dust far beyond Neptune and Pluto, so every observation could lead to a discovery,” says physicist Alex Doner of the University of Colorado Boulder.
“The idea that we might have detected an extended Kuiper Belt – with a whole new population of objects colliding and producing more dust – offers another clue in solving the mysteries of the Solar System’s most distant regions.”
The Kuiper Belt is characterized by a high density of rocky, icy objects (icy because it’s very far from the Sun, and very cold). It’s filled with large rocks and dwarf planets, and a whole bunch of objects that we can’t really see because they’re relatively small, and it’s very dark out there. But dust can tell us a fair bit about what’s going on.
The Kuiper Belt was already thought to be pretty huge. It starts at the orbit of Neptune, some 30 astronomical units from the Sun, and extends outward for an unknown distance. However, the inner main region was thought to peter out at about 50 astronomical units.
New Horizons is the NASA probe launched to explore the outer Solar System. It visited Pluto, which orbits the Sun at an average distance of 39 astronomical units, in 2015, and kept going. In January 2019, it flew by a strange object named Arrokoth, which orbits the Sun at an average distance of 44.6 astronomical units.
Since then, between distances of 45 and 55 astronomical units, New Horizons kept collecting data, assiduously beaming it back home to Earth. And guess what? Its Venetia Burney Student Dust Counter (SDC) is detecting way more dust than scientists expected there to be at that distance.
A high density of dust means there needs to be either extra dust is being produced or solar radiative forces are unexpectedly pushing dust from denser regions out into that space.
The most likely source of any extra dust would be interactions between larger objects – collisions, for example. That means there needs to be enough icy rocks out there that they come together with relative frequency.
More recent telescope observations have started to suggest that the inner main region of the Kuiper Belt might extend as far as 80 astronomical units, meaning the discovery is consistent with hints that the Kuiper Belt just might be larger than expected.
At time of writing, New Horizons is more than 58 astronomical units from the Sun. It’s now in its second extended mission, operating past initial expectations, and still sending data home. Scientists hope that it will last at least as far as 100 astronomical units, and perhaps, if we’re lucky, as far as the very edge of the Solar System, beyond 120 astronomical units.
“These new scientific results from New Horizons may be the first time that any spacecraft has discovered a new population of bodies in our Solar System,” says astronomer Alan Stern, New Horizons principal investigator of the Southwest Research Institute.
“I can’t wait to see how much farther out these elevated Kuiper Belt dust levels go.”
Hibernation used in conjunction with radiotherapy could be the key to fighting cancer in the future, according to new research.
Putting cancer patients into a hibernation-like ‘deep sleep’ state could hypothetically slow down their bodily functions and halt the spread of tumours inside their tissues, while also increasing the body’s resistance to radiation, scientists suggest.
The experimental treatment – which is still many years away from being attempted in humans – might sound like science fiction, but does have some grounding in reality.
Previous research involving rats showed that inducing hibernation by cooling their bodies down to 15 to 19 degrees Celsius (59 to 66.2 degrees Fahrenheit) not only slowed their metabolic functions – it also increased their radioresistance, or tolerance for radiation therapy.
Now, physicist Marco Durante from the Trento Institute for Fundamental Physics and Applications in Italy says the same approach could work for terminal cancer patients – and might be used in Stage 4 cancer cases, where tumours have spread too widely in the body for conventional therapies to be an option.
“You cannot treat all the metastasis – you cannot use surgery everywhere to remove the cancer or do radiation in all the affected parts of the body or you will kill the patients trying to destroy the cancer,” he said at the American Association for the Advancement of Science (AAAS) annual meeting in Boston on Sunday.
“But if you could put the patient into synthetic torpor [induced hibernation] you could stop the cancer growing. It gives you more time.”
While humans don’t have the ability to naturally hibernate the way that some animal species do, it’s an area of much interest to scientists – as figuring out a way to safely induce people into a state of suspended animation could have all kinds of applications, from medical treatments, to enabling safe, long-term space travel.
The potential of inducing hibernation in astronauts was the subject of Durante’s most recent research, and while it’s still a hypothetical area, the researcher says it’s just a matter of time before synthetic torpors become possible for humans.
“Now it is understood how it works, I’m confident we will be able to develop drugs that can induce this torpor,” he said.
“We are aiming for at least one week [of hibernation]. It gives us time to deliver all the treatments that are needed to make the person cancer-free.”
To make hibernation work in humans, Durante says human body temperature – usually about 37 degrees Celsius (98.6 degrees Fahrenheit) – would be dropped to around 13 to 15 degrees Celsius (55.4 to 59 degrees Fahrenheit).
At this temperature, with metabolic functions slowed to a crawl, the researchers suggest that damage to tissue sustained from high doses of radiation would be minimal.
In effect, this would make aggressive radiation therapy safe, while similar doses might kill an awake, non-hibernating patient.
While it’s a promising area for researchers to look into in future studies, other scientists say we should be careful not to get carried away with Durante’s comments.
For starters, we haven’t yet succeeded in coming up with a way to safely put people into hibernation. And even if we do, there’s no guarantee that we’ll see increased radioresistance like animal studies show – as of 2014, average rate of successful translation from animal models to clinical cancer trials was less than 8 percent.
“The effects of a technique like induced hibernation on cancers are hard to predict: they might help or hinder the treatments we use,” chief clinician at Cancer Research UK, Peter Johnson, told New Scientist.
“We will need to see some careful experiments in laboratory models before we can say whether this would be safe or effective for people.”
Undaunted, Durante thinks induced hibernation could be possible within the next decade or so.
“We can currently cure around 50 percent of cancers. The problem is the other 50 percent,” he said.
“If this approach works, there will be many of these patients with multiple metastases who will have hope. It will be a really huge step ahead.”
IMPORTANCE: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma.
OBJECTIVE: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor.
DESIGN, SETTING, AND PARTICIPANTS: This was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months’ follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023.
INTERVENTION: Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months.
MAIN OUTCOMES AND MEASURES: The primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only.
RESULTS: Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.
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