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500-Million-Year-Old Fossil Suggests Ocean Origin For Spiders

500-Million-Year-Old Fossil Suggests Ocean Origin For Spiders

Yahoo3 days ago
The special brains of spiders may have started to evolve in the oceans, long before their ancestors crawled onto land.
A fresh look at a 500-million-year-old fossil by researchers from the University of Arizona and Lycoming College in the US and King's College London has revealed remarkable similarities between the brains of extinct marine arthropods and modern-day arachnids.
The discovery wades into controversial territory regarding the evolutionary origin of spiders and their relatives.
Today, spiders, scorpions, mites, and ticks are virtually all terrestrial, and the prevailing view is that these arachnids evolved from a common, land-dwelling ancestor.
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Where that ancestor came from is a whole other mystery. Arachnids on land are related to other 'chelicerates' in the ocean, like sea spiders and horseshoe crabs, but the fossil record is very patchy.
"It is still vigorously debated where and when arachnids first appeared, and what kind of chelicerates were their ancestors, and whether these were marine or semi-aquatic like horseshoe crabs," explains University of Arizona neuroscientist Nicholas Strausfeld.
The transition from sea to land is a big step for a little creature, no matter how many legs it has.
The oldest accepted remains of an arachnid are of a 430-million-year-old scorpion, a critter that lived on land. But new evidence suggests that arachnids as a whole may have started to diverge from other chelicerates long before that.
On the outside, Mollisonia symmetrica may not look very 'spidery'. It kind of resembles a pillbug with a bunch of little legs, and previously, it was thought to be an ancestor of horseshoe crabs.
Using light microscopy, researchers have now imaged the fossil's central nervous system and come across an unexpected find.
The nervous system of Mollisonia doesn't resemble that of a horseshoe crab or even a crustacean or insect. Instead, the pattern of radiating neural centers was flipped backward, like that of an arachnid.
"The arachnid brain is unlike any other brain on this planet," explains Strausfeld.
In the Mollisonia fossil, the unique nervous system seems to innervate numerous legs, as well as two pincer-like mouth parts, where modern spiders now have fangs.
"This is a major step in evolution, which appears to be exclusive to arachnids," says evolutionary neuroscientist Frank Hirth from King's College London.
"Yet already in Mollisonia, we identified brain domains that correspond to living species… "
That seems to be no coincidence. Upon further statistical analysis, Hirth and colleagues have found that arachnids probably didn't evolve similar structures to Mollisonia by accident; they were more likely inherited.
If the team is right, that puts Mollisonia at the base of the arachnid lineage, making it a sister to horseshoe crabs and sea spiders.
While still speculative, it's possible that the unique brain structure seen in the Mollisonia lineage helped its later successors survive on land.
Neural 'shortcuts' to the legs and pincers, for instance, could make it easier to control and coordinate complex movements, like walking or weaving webs.
"We might imagine that a Mollisonia-like arachnid also became adapted to terrestrial life making early insects and millipedes their daily diet," theorizes Strausfeld.
Perhaps it was the earliest arachnids on land that first drove insects to evolve wings and hence flight – and maybe, in turn, airborne prey led to the evolution of webs.
From the ocean floor to the treetops, the way that arachnids have adapted to the changing times is truly enviable.
The study was published in Current Biology.
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Experts stunned after record-breaking surge in rare butterfly sightings: 'None of us want summer 2025 to ever end'
Experts stunned after record-breaking surge in rare butterfly sightings: 'None of us want summer 2025 to ever end'

Yahoo

timean hour ago

  • Yahoo

Experts stunned after record-breaking surge in rare butterfly sightings: 'None of us want summer 2025 to ever end'

Ecologists in West Sussex recently recorded a jaw-dropping 283 purple emperor butterflies in a single day at the Knepp Castle Estate, a 3,500-acre rewilding project in the county. It's an all-time high for the site — and a major milestone for the conservation of the vulnerable species, The Guardian reported. The purple emperor is noted for being an elusive butterfly species — and for having some unusual behavior. According to The Guardian, the pretty purple butterflies feed on dung and animal carcasses — or fermented tree sap that makes them "tipsy." It's an unexpectedly grotesque diet for a butterfly, especially one this breathtaking. Though the butterfly species is listed as wildlife of "least concern" by Great Britain's Red List, the species is listed as a "medium" conservation priority by Butterfly Conservation. That's because populations are dispersing and dropping due to habitat loss, a consequence of land development and rising global temperatures. And it's exactly why the large population sighting at Knepp is so exciting. According to The Guardian, experts attribute the boost in sightings to Knepp's pioneering "process-led" rewilding project. Started in 2001, the project transformed former farmland into a thriving natural habitat for the butterfly species. Rewilding projects are essential to supporting vulnerable wildlife and native plant life impacted by climate shifts and pollution. Knepp's rewilding project includes restoring natural habitats, reintroducing native wildlife and plant life, monitoring the area's ecosystem, and much more. This approach helps to restore natural ecosystems, boost biodiversity, and build resilience against future climate shifts. Rewilded landscapes — including forests, wetlands, and grasslands — can act as powerful carbon sinks, absorbing pollution from the atmosphere. These areas also help regulate water cycles and create more stable, self-sustaining environments, which are crucial in the face of a warming world. Particularly key to the purple emperor's resurgence is the growth of sallow scrub in the area, a crucial plant for the purple emperor's egg-laying, according to Rewilding Britain. Ecologists at Knepp say the plant has flourished, thanks to natural dispersal from roaming livestock like pigs and ponies. Knepp's butterfly expert, Neil Hulme, told The Guardian that purple emperor populations naturally fluctuate year to year, so it may be premature to celebrate. Still, he highlighted Knepp as a "top-quality rewilded landscape" — and not only for the purple emperor butterfly. Other butterfly species, including purple hairstreaks and the silver-washed fritillary, are also being sighted in similar record numbers in the area. Hulme told The Guardian Knepp has "clouds of butterflies everywhere," adding that "none of us want summer 2025 to ever end." Do you think America does a good job of protecting its natural beauty? Definitely Only in some areas No way I'm not sure Click your choice to see results and speak your mind. Join our free newsletter for good news and useful tips, and don't miss this cool list of easy ways to help yourself while helping the planet. Solve the daily Crossword

Is Silicon Valley Losing Its Influence on DC?
Is Silicon Valley Losing Its Influence on DC?

WIRED

time2 hours ago

  • WIRED

Is Silicon Valley Losing Its Influence on DC?

By Zoë Schiffer and Jake Lahut Jul 28, 2025 1:14 PM This episode of Uncanny Valley covers black holes, woke AI, and the relationship between Silicon Valley billionaires and the Trump administration. Peter Thiel speaks at The Cambridge Union on May 08, 2024, in Cambridge, Cambridgeshire. Photo-Illustration: WIRED Staff; Photograph:In today's episode, WIRED's director of business and industry, Zoë Schiffer, is joined by senior writer Jake Lahut to run through five of the most important stories we published this week—from Trump's newly unveiled AI plan to how supermassive black holes could have originated. Plus, they dive into why the relationship between Silicon Valley and DC is undergoing some major changes. Mentioned in this episode: Trump's AI Action Plan Is a Crusade Against 'Bias'—and Regulation by Kate Knibbs and Will Knight Newly Discovered 'Infinity Galaxy' Could Prove How Ancient Supermassive Black Holes Formed by Jorge Garay How Trump Killed Cancer Research by Elisa Muyl and Anthony Lydgate The Great Crypto Re-Banking Has Begun by Joel Khalili The GOP's Message for Tech Billionaires: Be Like Peter Thiel by Jake Lahut You can follow Zoë Schiffer on Bluesky at @zoeschiffer and Jake Lahut on Bluesky at ‪@ Write to us at uncannyvalley@ How to Listen You can always listen to this week's podcast through the audio player on this page, but if you want to subscribe for free to get every episode, here's how: If you're on an iPhone or iPad, open the app called Podcasts, or just tap this link. You can also download an app like Overcast or Pocket Casts and search for 'uncanny valley.' We're on Spotify too. Transcript Note: This is an automated transcript, which may contain errors. Zoë Schiffer: Hey, this is Zoë. Before we start, I want to tell you about the new WIRED subscription program. If you're already a subscriber, thank you so much for supporting us. If you haven't signed up yet, this is a great time to do so. You'll have access to newsletters with exclusive analysis from WIRED reporters and access to live stream AMAs where you can ask your most pressing questions. Head over to to learn more. Welcome to WIRED's Uncanny Valley . I'm WIRED's director of business and industry, Zoë Schiffer. Today on the show, we're bringing you five stories that you need to know about this week. And later we'll dive into our main segment on how the influence of Silicon Valley is shifting in D.C. And why Republicans think tech leaders should follow the example of Peter Thiel. I'm joined today by WIRED's senior writer, Jake LaHut. Jake Lahut: Hey, Zoë, great to be with you. First time. Zoë Schiffer: Jake, you and I were both watching Trump's speech yesterday. This was a keynote speech that he gave, an event that was hosted by the All-In Podcast, and he was talking about AI regulation. This came after he had already put out an AI action plan, which was this really long document that outlined 90 plus policies focusing on three main goals. Accelerating AI innovation, building AI infrastructure, and leading international diplomacy and security. So I guess just to start, can I get your high level take on the speech? Because I don't watch Trump a ton. And every time I do, I'm really struck by his just vibe is so fascinating and so funny to me. Jake Lahut: Oh, absolutely. So to give the listeners a little bit of background on where I come from. I have been to more Trump rallies than I can count, in person that is, covering them in a professional capacity. And the weird thing about seeing Trump speak is you can really get a feel for, one, how much he just wants to be there. And this was definitely a case of he didn't seem like he really wanted to be doing this speech. There's this difference in the cadence and tone of his voice where even if you're not watching it, where you can see him looking at the teleprompter and then looking away to riff, he has this very rote cadence when he's reading on the prompter. So I would say this was a pretty middle of the road Trump phoning it in type speech. Zoë Schiffer: Yeah. I had a one-on-one at the beginning of the speech and the person I was supposed to talk to was like, "Wait, should we cancel it? Should we push it back?" I was like, "It's Trump. I feel pretty confident that he's not going to start talking about AI until like 30 minutes in." But he really was talking about rolling back any level of regulation that we already have and definitely not imposing new regulations on AI companies, really trying to move away roadblocks so they can go innovate as quickly as possible. He framed it as an all-out race. And he talked a lot about woke AI. So maybe let's get into that a little bit because this is a sticking point for him. Jake Lahut: Yeah. And I still don't really know what he means by woke AI. I mean, we did see at the outset of some of these models, I guess going back to 2022, '23, I remember Google's had those weird renditions of the founding fathers where there were very few, if any, white ones. Maybe he's talking about that. But I'm also wondering, is he talking about going full Grok with what we're going to be supporting? And then the other thing that I just on a very high level that I found interesting was he's basically saying China doesn't play by the rules. And if they're not going to play by the rules and we want to beat China, then we can't play by any rules either. And he extends that to saying we shouldn't even be paying publishers or anyone whose work is trained not to... He had this example of like, well, you read a book and you learn something from the book, but that doesn't mean anybody should get paid. And I was like, okay. Zoë Schiffer: Right. Jake Lahut: And also, I've worked at least three publications now where my work has trained these models and I have not seen a dime. So, yeah, I was a little stupefied, to be honest, hearing that part. Zoë Schiffer: Yeah. Our Slack was absolutely blowing up when he was- Jake Lahut: It was. Zoë Schiffer: ... redefining fair use in real time. Everyone was losing their minds. So speaking of the current administration, our next story deals with its role in a critical field, which is cancer research. Our colleagues, Elisa Muyl and Anthony Lydgate analyzed how the Trump administration has erased hundreds of millions of dollars that were supposed to be used, and were being used, for cancer research. Specifically, the administration has paused an estimated $1.5 billion in funding to the National Institutes of Health, or NIH, which is the largest funder of cancer research in the world. And they've also effectively halted clinical trials of new drugs and laid off thousands of employees at the FDA and NIH and the Centers for Disease Control and Prevention. And, get this, Trump officials have reportedly maintained a list of flagged keywords that they believe should trigger program reviews. Of the NIH grants terminated so far, the 50 most common flag keywords were things like, you might expect unfortunately, trans, expression, diverse, and women. Jake Lahut: On the one hand, not surprised. But also this is the kind of thing that I do wonder how much it ends up penetrating into the actual news diets of folks who are not following this really closely. And when you look at the pie chart that we have in this story, just the sheer amount of this that's coming from Harvard is really quite staggering. And the weird part of this that's very different from Trump 1.0, it's like AI scraping meets his personal vendettas and we get these really strange results. Zoë Schiffer: Yeah. It's really interesting because I feel like there are things that, I've thought about this with Elon Musk specifically a lot. It's like he has thrived in environments where his actions, and he's an impulsive risk-taking person, have a pretty quick consequence. He can see feedback really quick. If he does something and it doesn't work, he can then pivot. But when you're in government, you don't get to see the impact of what you're doing for kind of a while. And so if cancer research grinds to a halt because of what the Trump administration is choosing not to fund or what Elon Musk's DOGE team decided to slash contracts for or funding for, we won't actually feel the impact of that for years. But the impact will be pretty devastating, you can imagine. Jake Lahut: Yeah. And even the longer term, second, third order effects of this. The brain drain aspect, I think, is going to be a very big story of this administration where think about if you're an undergrad who's looking at master's, PhD type research, it's like where are you going to go? Are you going to try to pivot your talents and go to the European Union? Are you going to just get a consulting job or try to go on Wall Street? I think that these are really difficult conversations that a lot of these researchers probably never thought they would have in what I would imagine for a lot of them is a very demanding but fulfilling field to try to literally cure cancer. Zoë Schiffer: Totally. Okay. I need to shift us to a new topic because I'm already feeling quite depressed. This one is about outer space. So my first question for you is how do you feel about outer space, Jake? And would you go if you had the chance? Normally I would say, no, thank you. I'm not interested. But I don't know after this maybe, yeah, take me to Mars. Jake Lahut: Weirdly, I would probably be more comfortable going to outer space than doing deep ocean exploration. That could be a recency bias with the- Zoë Schiffer: I was going to say. Jake Lahut: ... the Ocean Gate thing. But no, I was super into the, not just the Apollo missions, but Gemini and Mercury as a kid. I had a little beanbag chair in my house where I would pretend it was the capsule- Zoë Schiffer: Oh, my gosh. Jake Lahut: ... that was reentering the atmosphere looking for all- Zoë Schiffer: I can picture this perfectly. Jake Lahut: Yeah. So huge Al Shepard, John Glenn fan. I love all that stuff. But I am also a rather large person, and I think the fitting into the vessel would be difficult. Zoë Schiffer: Totally fair. I can't 100% guarantee you would see this if you did find a vessel that could take you, but WIRED contributor Jorge Garay reported that a team of astronomers from Yale and Copenhagen recently discovered two galaxies colliding with each other. They have called it the Infinity Galaxy. And this finding is pretty exciting because it could be the first direct evidence of how really old supermassive black holes were formed. Jake Lahut: Yeah. This is some interstellar type stuff, but it really does look like that sideways eight formation. And I found this pretty mind-blowing. Especially in our vertical video treatment of it, if you want to check this out on Instagram Reels. It's rather mesmerizing, I got to say. Zoë Schiffer: So the prominent theory of how they form is when stars run out of fuel and collapse under their own gravity. But with very old supermassive black holes, there wouldn't have been enough time for the stars to get to that point. So this Infinity Galaxy supports another theory that they were able to form from dense clumps of matter, so no star busting needed. Jake Lahut: At least for now, we are still discovering new things about science in the United States of America. And maybe that'll continue, maybe it won't. Zoë Schiffer: Well, if not, AI apparently is going to step in and do everything for us. Jake Lahut: DOGE can't go out there and catch up to the James Webb telescope at least. No one's catching that bad boy anytime soon. Zoë Schiffer: Okay. So our next story takes us back to earth and, honestly, back to the Silicon Valley elite of it all. Our colleague, Joel Khalili, reported that crypto firms are finally getting more access to banking. This is actually critically important and covers both of our areas of reporting, Jake, because de-banking was a core reason that a lot of the Marc Andreessen types in the world really soured on the Biden administration and went all in on Trump. So now we're kind of seeing the fruits of that decision play out because under the crypto-friendly Trump administration, a number of US FinTech firms are competing to offer bank accounts to these crypto firms. But they still do need to follow the ground rules set by the partner bank involved, so there's no fully escaping the traditional banking system. But curious on your take here given how critical this was to the last election. Jake Lahut: Oh, yeah. I mean, if you've ever had the pleasure of hearing Don Jr. talk about this, he gets real worked up about the de-banking. From my sourcing perspective, I remember being at the Republican convention last summer in Milwaukee, and I remember the second day there I'm bumping into some people I recognize. And every time I'm like, "Hey, what are you doing here? You're not on the Trump 2024 campaign." And maybe they were on it in 2016 or 2020. And it was like, "Nah, dude, I'm here with crypto. Yeah, check out this party later." Every time. And I'm like, "When did all of you end up working for these crypto companies?" But you got to think in the context of after January 6th, if you were a Trump former White House official or you were on those campaigns, your cash-out options by usual D.C. swamp standards were very different. So you weren't going to be going to K Street and doing lobbying in the traditional sense. You weren't going to be getting those cuss jobs on some Wall Street legislative affairs team or whatever. So for a lot of them, this was kind of the only game in town. And that's where I find this development really interesting is could this end up affecting that Republican talent cash-out pipeline in some weird way? And I remain completely perplexed about the next phase that Congress is going to try to set up some sort of market securities framework for these cryptocurrencies where right now they've basically given them the stablecoin win. Zoë Schiffer: Exactly. Okay, one more before we go to break. Yesterday we published a story about the former DOGE offices at the General Services Administration in Washington D.C. We had gotten a little tip that they were left a bit of a mess when DOGE started to vacate said offices. Near the space where DOGE previously operated, there were stacks of mattresses that still had sheets on them, there were box springs, and then there was a whole corner of baby toys. Jake Lahut: A lot, yeah. Zoë Schiffer: A lot. We ended up publishing this story on kind of the scene, and we basically just published a bunch of photos of what we saw. Jake Lahut: Well, Zoë, I think you're selling yourself short because your writing and narrative description of this scene was just something to behold. And I really think you got to read it online because the pictures are rather stunning. And I guess I would call this Dude Bro Chernobyl or something like that, where it was just like, whoa, this is the aftermath of something real serious going on here. Zoë Schiffer: I wish I'd had that line. Coming up after the break, we dive into Jake's inside scoop on how the influence of Silicon Valley has been slowly but surely shifting in D.C. Stay with us. Welcome back to Uncanny Valley . I'm Zoë Schiffer. I'm joined today by WIRED's senior writer Jake LaHut, who recently reported on the alliance between the Republican Party and Silicon Valley and how it's still going strong, but it's actively changing. Jake, this has been a long, long year so far. But it wasn't that long ago that Elon Musk was Trump's right hand, and tech leaders like Tim Cook and Jeff Bezos were attending the presidential inauguration. So what the heck has changed? Jake Lahut: Well, I think both sides of the equation here are starting to figure each other out a little more. But based on the Republican strategists and people around Trump world I talk to, I think that at the moment they feel as if they have the better end of the deal here where they got all this money that helped them rise to power and they don't feel necessarily too exploited by the tech community. But also there are a lot of lessons learned from Elon's crash out. And the main one, as strategist put this pretty succinctly, where he has this old axiom of the podiums are for the principals. The principals being the candidate, your lawmaker. And Elon really needed to stay off the podium. And because he publicly attached himself to this thing so much, especially with that Wisconsin Supreme Court race where he was out there campaigning for it. And that kind of gave the Trump White House, and Republicans more broadly, a classic AB case study of like, okay, clearly he was a drag on the party brand here. And some of these strategists think that that's going to also hurt the Republicans to some degree in the midterms no matter what they do. So that's where it gets interesting with folks like Peter Thiel and, I think, the evolving thinking of keep it behind the scenes and, more importantly, don't put all of your bets in terms of donations on a couple of candidates or in this VC mindset on safe seats. And instead, this notion of being a team player keeps coming up. House Republicans, consultants, they want the Silicon Valley donors to really spread the wealth around and to try to just shore up Republicans for the midterms. Zoë Schiffer: Right, right. Because Peter Thiel is massively influential, but he's not centering himself all the time. It's rare that he actually gives interviews. He's not super outspoken on social media. So he's more of this shadowy figure, which is a huge contrast to Elon Musk who really made himself the main character in the Trump administration. Jake Lahut: Yeah. And obviously the exception to Thiel being behind the scenes would be this interview we referenced in the story with Ross Douthat of the New York Times, where he got into all sorts of zany wild stuff. But for the most part, he's really kind of Mr. Incognito, especially among the Republican base. So we had a source in the story basically saying most voters don't know who the fuck Peter Thiel is, and that works to their advantage. Zoë Schiffer: It's so interesting because I feel like one thing that happened with all of these tech leaders and Biden was that they felt like the relationship, the promise had broken down. They were being supportive, they were giving money- Jake Lahut: Yes. Zoë Schiffer: ... and yet the Biden administration, and Biden in particular, were coming out and really slamming them and going after them. There were investigations, they had Lina Khan who was targeting them for alleged antitrust violations. So it felt like a very hostile dynamic. And I think when they looked at Trump, they were like, maybe they disagreed with him on a number of policies, but it felt very pay to play. They were like, if I support him, if I put in money, I kind of know what I'm going to get. But I'm curious if you think that that part of their equation has actually worked out for them so far. Jake Lahut: Yeah. This is where I think there's a learning curve for not just the Silicon Valley billionaires, but these broader, newer donors from the tech world where they have that kind of VC disruptor return on investment mindset. And the Republican consultants and strategists who I talk to are describing to me how you kind of got to sit these guys down and be like, "Look, you can't just come in here and say I give you X amount of money, you give me Y." You need to be involved in the longterm, and maintaining this relationship is good for both of us. There was a quote that didn't make into the story where someone said that there's probably like a 5% range of politicians where if you add a zero to the donation, they will do exactly what you want. But most of these guys have been in the game long enough, if you're a House Republican, Capitol Hill or whatever, where you really can't be tipping your hand too much with that pay to play thing. And this is sort of the ongoing re-education of the valley from Republicans about how this stuff actually works. Zoë Schiffer: I can feel that as a headline for one of your future calls. Jake Lahut: Thank you. Zoë Schiffer: It feels like the crypto wing is still super important to the Republican Party. A source told you that crypto might be the glue that is keeping the tech world tied to politics. Is that what you're hearing from sources? Jake Lahut: Yeah. And I think that that's twofold. One is obviously that it remains very profitable for the Trump family in terms of the mean coins and all that. And then the other is just the sheer amount of money they were able to pump in with these packs. And I think what's very distinct about the crypto donations is that most industries, take oil and gas or your typical Republican money machines, they want to advertise about their issue in their industry. The crypto money that came in, a lot of it went towards stuff that was totally unrelated to cryptocurrency, and that ended up being very valuable and flexible for Republicans. However, a lot of the folks who are giving this money in the crypto space were kind of like apolitical libertarians, and I think now they're a little confused, a little impatient. And another quote we had in the story was that there's just a lot of bumbling and fumbling among the crypto crowd. Were they've really got to do a lot of catching up compared to the other sub industries coming out of the valley. Zoë Schiffer: Right, right. So the GOP seems to be doing this balancing act of keeping the tech industry close while maintaining just enough distance to avoid crash-outs like the one that we saw with Elon Musk. So what's at stake for them as they navigate this? Jake Lahut: It's hard to make a prediction about the midterms and the impact that any potential drop-off in donations or whatever would have there. But in terms of the Trump base, which is already going through it with the Jeffrey Epstein saga, I think they've got to be careful about broadcasting and telegraphing too much chumminess and proximity here. There's a reason why the Biden White House decided to have this posture against big tech because they believe that most Americans, and certainly a lot of independent voters, have become much more skeptical and distrustful of just this broad notion of big tech. So when you look at someone like JD Vance who kind of has this whole money train on lock, at least to start out, going into the 2028 Republican Presidential primary where the base, and by the base I mean people who vote in Republican primaries, they tend to be very distrustful of elites any sort. And suddenly JD is going to be the establishment and his connections with Peter Thiel and all these things are going to be more threaded over and more well known. So that would be the bigger risk, I think. It's more of a vibe aspect than the money train. Zoë Schiffer: Jake, thank you so much for joining me today. Jake Lahut: Great to be with you, Zoë. Thanks so much. Zoë Schiffer: That's our show for today. We'll link to all the stories we spoke about in the show notes. Make sure to check out Thursday's episode of Uncanny Valley which is about the growing industry of brain-computer interfaces. Adriana Tapia produced this episode. Amar Lal at Macrosound mixed this episode. Pran Bandi is our New York Studio engineer. Kate Osborn is our executive producer. Condé Nast head of global audio is Chris Bannon. And Katie Drummond is WIRED's global editorial director.

What to Know About Infusion Therapies in Parkinson's Disease
What to Know About Infusion Therapies in Parkinson's Disease

Medscape

time3 hours ago

  • Medscape

What to Know About Infusion Therapies in Parkinson's Disease

This transcript has been edited for clarity. Indu Subramanian, MD: Hi, everyone. This is Dr Indu Subramanian, from UCLA. I'm excited to have you join us at Medscape today. I'm delighted to have my friend and close collaborator, Professor Ray Chaudhuri, join us from Europe. He's a professor of neurology at King's College London and King's College Dubai. He's a groundbreaking clinician who's really changed the field of movement disorders and Parkinson's. He's introduced us to many novel therapies over the years and set the stage for nonmotor Parkinson's disease. It's been a pleasure to learn from him over the years. I'm excited to have him teach us about the many options in the infusion therapy world. Welcome, Ray. K. Ray Chaudhuri, MD, DSc: Hi, Indu. Thank you for having me. Infusion Therapies Subramanian: One of the things that we wanted to talk about today was infusion therapies, including subcutaneous foslevodopa/foscarbidopa. There's also been, as you know, a longstanding history that you've had exposure to of apomorphine pumps, Duopa pumps, and the patch. Chaudhuri: Infusion therapies have been a mainstay, shall we say, underpinned advanced therapies for Parkinson's for a long time. In fact, originally it was developed in the 1970s, but commercially, I think the first sighting of infusion therapy in Parkinson's, certainly in Europe and in the UK, came in the 90s with apomorphine: apomorphine infusion and injection. I understand apomorphine injection is available, and apomorphine infusion has recently been made available in the US. The subcutaneous field developed into infusion of levodopa, and there are two forms. The first one, commercially available now in many countries in the world, is the foslevodopa/foscarbidopa preparation, which is an approved drug of levodopa and carbidopa. When infused with this very small Vyafuser pump, it immediately gets converted to levodopa and carbidopa in the skin and is then absorbed and provides continuous nerve stimulations over 24 hours. Another form, is the NeuroDerm product, which is levodopa infusion with carbidopa, not foslevodopa/foscarbidopa. That's infused with a different pump system with two syringes, but that's not yet commercially available. The one that's commercially available is foslevodopa/foscarbidopa, and there is an accumulated experience of over 67,000 patients in the world now with the use of this product. It is novel in the sense that it's the first time ever levodopa has been made available to be given in a subcutaneous infusion format. It was previously available as intrajejunal levodopa with levodopa/carbidopa, Duodopa or Duopa. Now, it's available subcutaneously, and the great advantage is that it's much less invasive. It doesn't require a surgery, which you needed with the Duodopa. Third, it is probably the only treatment option at the moment that really effectively gives you a 24-h treatment option, so it gives you treatment option during the day and through the night. The other additional advantage of this very sophisticated pump is that it allows you to do the setting high and low. For instance, you can set the dosing at a high level during the day, depending on the patient's requirements, and then cut the dose down at night about 30%, which is your normal dopaminergic neurotransmission as it occurs during the sleep-wake cycle. It has great advantages also over the early morning OFF periods, which many other therapies do not really affect, because they're usually effective for only 14 hours. You don't get that cover all through the early morning periods when the patients are often OFF. They wake up with severe, dystonic pain, difficulty turning in bed or passing urine, urgency, and even depression or other nonmotor fluctuations that might occur. All of that seems to be helped by the use of foslevodopa/foscarbidopa. Infusion vs DBS Subramanian: Sleep is so important in our patients. I think we've really under-recognized that. You've been doing a large amount of work and even put a whole collection of articles together on sleep. It's just pretty amazing how little we have to offer patients in the sleep realm, and it can affect, presumably, cognition, daytime symptoms of motor and nonmotor issues, and quality of life both for the patient and their caregivers who are also not getting sleep. In the landscape currently of infusion therapy and deep brain stimulation (DBS), you have DBS available in the UK as well as other parts of Europe, along with these infusion therapies. You've had these infusion therapies for much longer than we've had in the United States, for example. Can you tell me a little bit about the decision algorithm if you have a patient in front of you, what type of patients do you send to DBS? Chaudhuri: Great question. Before I go into the DBS option, I think you mentioned a really important part, which is sleep. I think sleep is often under-recognized. It's part of this dashboard of Parkinson's, which we introduced, and we should be recommending at least 6-8 h of sleep per day because of the activation of the glymphatic system and potential effect on amyloid clearance. Any treatment option like foslevodopa/foscarbidopa, which is helping this early morning OFF period — and we've shown that in two long-term studies— actually helps with sleep, because it cuts down the fragmentation of sleep in early morning and, therefore, helps you have a good quality of sleep, which will then indirectly affect the issues around cognition and so on. That sort of study will need to be done in the future, but it's an enormously new development and a great advantage of this 24-h therapy. In relation to an algorithm, in addition to DBS and apomorphine, now we have foslevodopa/foscarbidopa, levodopa infusion into the jejunum with Duopa, but also LECIG gel, which is levodopa/carbidopa/entacapone infusion. That's also available in some countries in Europe. In terms of when, ideally, you would choose DBS, my algorithm would suggest the age parameter. Most centers would operate up to 70 years of age. After 70, it becomes a little bit tricky. It depends on the local surgeon's preference and the patient's condition. If you look at people below age 70, if they have clear dyskinesia as the dominant problem or pharmacoresistant tremors, in that situation, I would go with DBS first. That seems to be very effective and a quick fix. Now, the data would also suggest patients must be given an option of subcutaneous therapy. Some patients might want to try the subcutaneous option first, which also works for dyskinesia, and specifically works very well for early morning OFF and sleep. They may say: What if I try that first, and if that doesn't work, I can still have DBS? Over the age of 70, at this moment in time, foslevodopa/foscarbidopa infusion would probably be the first choice, given that apomorphine has dopamine agonist side effect issues, such as somnolence, postural hypertension, and the potential for impulse control disorder. I would think most people would go with the levodopa-based option, but there are, of course, situations where you might want to use apomorphine. If somebody's very profoundly depressed or is very anhedonic or apathetic, you might want to try apomorphine first because of it's antagonist effect, which helps with apathy and depression. Below the age of 70, if a patient has dominant problems with bad dyskinesia, troublesome dyskinesia, diphasic dyskinesia, ballistic dyskinesia, along with pharmacoresistant tremor, probably DBS is the first option. Such a patient should also be given the option of subcutaneous therapy, and they might actually choose subcutaneous levodopa or foslevodopa/foscarbidopa first because it also has antidyskinetic action after an initial period when the dyskinesias might be there. After a few weeks, there's a delayed effect, the dyskinesias tend to go down. If that doesn't work or if the patient develops skin issues or neuropsychiatric problems, DBS can still be an option. Over the age of 70, however, we would probably go for a subcutaneous option first. The majority of patients will probably choose levodopa, but apomorphine remains a potential option if the patient's severely depressed or apathetic. You want to give apomorphine and agonist properties a little try first. Skin Side Effects Subramanian: You mentioned skin issues. Could you describe those a little bit? Chaudhuri: With any subcutaneous anti-parkinsonian treatment, skin problems become an issue with chronic therapy. It was an issue with apomorphine. Apomorphine causes nodules and you have to be aware of that and take action so that you don't get these nodules or reduce the frequency. With foslevodopa/foscarbidopa, the situation is a little bit different because of the pH issue and possibly because there's some skin intolerance with levodopa. We had recently suggested that there are asymptomatic skin problems and symptomatic skin problems. Among the symptomatic skin problems, you can get redness or a little bit of inflammation around the area. Very rarely, that might develop into cellulitis. That's what we must prevent. You can take preventive actions. For instance, you can use a low pH soap water wash. You can change the needles daily. You can keep the skin area very clean. At the first sign of any inflammation or infection, use a combination of antibiotics and perhaps some steroids as well. These are potential steps you can take, but that's something to remember. I think with good management, it should not be a major issue. The other side effect problem that you might get is neuropsychiatric problems. We have noticed this, and it might be related to the overnight infusion. What one might have to do is cut down the dose of the overnight infusion — and in very selected, rare cases — even stop the nighttime infusions for a few days and then restart it. That tends to sort the problem out. In some cases, you might need to use a drug such as quetiapine. When you're selecting a patient, therefore, it's important to screen for this or keep in mind the use of nighttime infusion and the prospect of any psychosis issues. Subramanian: That makes sense. Preventing hallucinations by not infusing as much medicine or no medicine overnight could be an option. This type of therapy gives you some flexibility there, which sounds great. I think this has been really edifying to me. I love learning from you. Thank you so much for joining us in your busy day there. We appreciate viewers out there on Medscape joining us as well.

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