Preclinical and Emerging Clinical Evidence Supporting the Translational Potential of GLP-1 Receptor Agonists for Treating Psychostimulant and Nicotine Use Disorders

Psychostimulant use disorder (PSUD) and nicotine use disorder (NUD) affect tens of millions of people worldwide, yet no clinically-approved medications exist for PSUD and existing NUD treatments have limited long-term efficacy. Recent preclinical evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists could be repurposed for treating PSUD and NUD. This review summarizes the current literature investigating the efficacy of GLP-1R agonists to reduce psychostimulant and nicotine-mediated behaviors in animal models of PSUD and NUD, respectively.

Role of Technology Acceptance in the Telerehabilitation of Patients With Metabolic Syndrome: Longitudinal Study

<strong>Background:</strong> The advent of telerehabilitation has created new opportunities for the care of patients with metabolic syndrome. In distant rehabilitation, technology acceptance is particularly important because home-based projects are based on digital devices, and many patients are less familiar with their use. <strong>Objective:</strong> Our aim was to explore technology acceptance among patients undergoing a 3-month complex, telemedicine-supported metabolic rehabilitation. We were curious to see how different factors influence the intention to use rehabilitation technologies and how this changes through the telerehabilitation process. <strong>Methods:</strong> Participants were selected from patients in the metabolic telerehabilitation program at the university. Our model was based on the unified theory of acceptance and use of technology 2, which we supplemented with various other constructs. A paper-pencil questionnaire survey was administered on the last day of the preparatory week of the rehabilitation program (T1, n=145) and at the follow-up visit after the closing (T2, n=139). We used structural equation modeling with the least squares method to explore the relationships between model variables. Respondent segments were also identified by performing a hierarchical cluster analysis using Ward’s method. <strong>Results:</strong> Facilitating conditions (FC) have the greatest impact (0.366) on the behavioral intention (BI) to use technology. Effort expectancy has no direct effect on BI; it operates only through performance expectancy (PE), which may be because, in telerehabilitation settings, patients are more goal-driven than experience-driven. The analyses of the T2 data show that the direct impact of social influence on BI has disappeared by the end of the rehabilitation process. This can be explained by the fact that during device use, it becomes clear that the devices are secure and the data are safe, making this factor implicit in the patient’s behavior. Only 2 constructs appeared in both the T1 and T2 models: PE and FC. By comparing the 2 datasets, we have provided empirical support for an old hypothesis: the experience of using the tool for a time has led to a significant reduction in the impact of FC and a corresponding increase in the dominance of PE, which has “absorbed” the impact of some other constructs. Based on respondents’ attitudes, we found 3 clusters. The telerehabilitation program itself has a significant impact on patients’ BI, as the relative share of “enthusiastic users” (73/145, 50.3%) increased by about 20%, while the share of “distrustful reluctants” (25/145, 17.2%) decreased to a quarter by the end of the program. <strong>Conclusions:</strong> This behavior-based functional approach enables treatments to be tailored to actual technology-use demands rather than to presumptive societal features. This means that before beginning rehabilitation, attempts should be undertaken to identify patients’ clusters in clinical practice, and rehabilitation should be planned according to the individual’s attitude toward technology.
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The shock of seeing your body used in deepfake porn 

When Jennifer got a job doing research for a nonprofit in 2023, she ran her new professional headshot through a facial recognition program. She wanted to see if the tech would pull up the porn videos she’d made more than 10 years before, when she was in her early 20s. It did in fact return some of that content, and also something alarming that she’d never seen before: one of her old videos, but with someone else’s face on her body.

“At first, I thought it was just a different person,” says Jennifer, who is being identified by a pseudonym to protect her privacy. 

But then she recognized a distinctly garish background from a video she’d shot around 2013, and she realized: “Somebody used me in a deepfake.”

Eerily, the facial recognition tech had identified her because the image still contained some of Jennifer’s features—her cheekbones, her brow, the shape of her chin. “It’s like I’m wearing somebody else’s face like a mask,” she says. 

“It’s like I’m wearing somebody else’s face like a mask.”

Conversations about sexualized deepfakes—which fall under the umbrella of nonconsensual intimate imagery, or NCII—most often center on the people whose faces are featured doing something they didn’t really do or on bodies that aren’t really theirs. These are often popular celebrities, though over the past few years more people (mostly women and sometimes youths) have been targeted, sparking alarm, fear, and even legislation. But these discussions and societal responses usually are not concerned with the bodies the faces are attached to in these images and videos.

As Jennifer, now 37 and a psychotherapist working in New York City, says: “There’s never any discussion about Whose body is this?” 

For years, the answer has generally been adult content creators. Deepfakes in fact earned their name back in November 2017, when someone with the Reddit username “deepfakes” uploaded videos showing faces of stars like Scarlett Johansson and Gal Gadot pasted onto porn actors’ bodies. The nonconsensual use of their bodies “happens all the time” in deepfakes, says Corey Silverstein, an attorney specializing in the adult industry. 

But more recently, as generative AI has improved, and as “nudify” apps have begun to proliferate, the issue has grown far more complicated—and, arguably, more dangerous for creators’ futures. 

Porn actors’ bodies aren’t necessarily being taken directly from sexual images and videos anymore, or at least not in an identifiable way. Instead, they are inevitably being used as training data to inform how new AI-generated bodies look, move, and perform. This threatens the livelihood and rights of porn actors as their work is used to train AI nudes that in turn could take away their business. And that’s not all: Advancements in AI have also made it possible for people to wholly re-create these performers’ likenesses without their consent, and the AI copycats may do things the performers wouldn’t do in real life. This could mean their digital doubles are participating in certain sex acts that they haven’t agreed to do, or even that they’re perpetrating scams against fans. 

Adult content creators are already marginalized by a society that largely fails to protect their safety and rights, and these developments put them in an even more vulnerable position. After Jennifer found the deepfake featuring her body, she posted on social media about the psychological effects: “I’ve never seen anyone ask whether that might be traumatic for the person whose body was used without consent too. IT IS!” Several other creators I spoke with shared the mental toll that comes with knowing their bodies have been used nonconsensually, as well as the fear that they’ll suffer financially as other people pirate their work. Silverstein says he hears from adult actors every day who “are concerned that their content is being exploited via AI, and they’re trying to figure out how to protect it.” 

One law professor and expert in violence against women calls these creators the “forgotten victims” of NCII deepfakes. And several of the people I spoke with worry that as the US develops a legal framework to combat nonconsensual sexual content online, adult actors are only at risk of further injury; instead of helping them, the crackdown on deepfakes may provide a loophole through which their content and careers could be stripped from the internet altogether.

How deepfakes cause “embodied harms”

During his preteen years in the 1970s, Spike Irons, now a porn actor and president of the adult content platform XChatFans, was “in love” with Farrah Fawcett. Though Fawcett did not pose nude, Jones managed to get his hands on what looked like pictures of her naked. “People were cutting out faces and pasting them on bodies,” Irons says. “Deepfakes, before AI, had been going around for quite a while. They just weren’t as prolific.”

The early public internet was rife with websites capitalizing on the idea that you could use technology to “see” celebrities naked. “People would just use Microsoft Paint,” says Silverstein, the attorney. It was a simple way to mash up celebrities’ faces with porn. 

People later used software like Adobe After Effects or FakeApp, which was designed to swap two individuals’ faces in images or videos. None of these programs required serious expertise to alter content, so there was a low barrier to entry. That, plus the wealth of porn performers’ videos online, helped make face-swap deepfakes that used real bodies prevalent by the 2010s. When, later in the decade, deepfakes of Gal Gadot and Emma Watson caused something of a broader panic, their faces were allegedly swapped onto the bodies of the porn actors Pepper XO and Mary Moody, respectively.

But it wasn’t just high-profile actors like them whose bodies were being used. Jennifer was “a very minor performer,” she says. “If it happened to me, I feel like it could happen to anybody who’s shot porn.” Since he started his practice in 2006, Silverstein says, “numerous clients” have reached out to report “This is my body on so-and-so.” 

Both people whose faces appear in NCII deepfakes and those whose bodies are used this way can feel serious distress. Experts call this type of damage “embodied harms,” says Anne Craanen, who researches gender-based violence at the UK’s Institute for Strategic Dialogue, an organization that analyzes extremist content, disinformation, and online threats. 

The term reflects the fact that even though the content exists in the virtual realm, it can cause physiological effects, including body dysmorphia. The face-swapped entity occupies the uncanny valley, distorting self-perception. After discovering their faces in sexual deepfakes, many people feel silenced, experts told me; they may “self-censor,” as Craanen puts it, and step back from public-facing life. Allison Mahoney, an attorney who works with abuse survivors, says that people whose faces appear in NCII can experience depression, anxiety, and suicidal ideation: “I’ve had multiple clients tell me that they don’t sleep at night, that they’re losing their hair.” 

Independent creators aren’t just “having sex on camera.” For someone to rip off their work “for their own entertainment or financial gain fucking sucks.”

Though the impact on people whose bodies are used hasn’t been discussed or studied as often, Jennifer says that “it’s just a really terrible feeling, knowing that you are part of somebody else’s abuse.” She sees it as akin to “a new form of sexual violence.”

The uncertainty that comes with not being aware of what your body is doing online can be highly unsettling. Like Jennifer, many adult actors don’t really know what’s out there. But some devoted followers know the actors’ bodies well—often recognizing tattoos, scars, or birthmarks—and “very quickly they bring [deepfakes] to the adult performer’s attention,” says Silverstein. Or performers will stumble upon the content by chance; some 20 years ago, for instance, the first such client to tell Silverstein her body was being used in a deepfake happened to be searching Nicole Kidman online when she found that one of the results showed Kidman’s face on her porn. “She was devastated, obviously, because they took her body,” he says, “and they were monetizing it.” 

Otherwise, this imagery may be found by an organization like Takedown Piracy, one of several copyright enforcement companies serving adult content creators. US copyright violations can be challenging to prove if someone’s body lacks distinguishing features, says Reba Rocket, Takedown Piracy’s chief operating and marketing officer. But Rocket says her team has added digital fingerprinting technology to clients’ material to help flag and remove problematic videos, often finding them before clients realize they’re online. 

By capturing “tens of thousands of tiny little visual data points” from videos, digital fingerprinting creates unique corresponding files that can be used to identify them, Rocket says—kind of like an invisible watermark. The prints remain even if pirates alter the videos or replace performers’ faces. Takedown Piracy has digitally fingerprinted more than half a billion videos and the organization has gotten 130 million copyrighted videos taken down from Google alone (though, of those videos, Rocket hasn’t tracked how many of these specifically include someone else’s face on a performer’s body). 

Besides copyright, a range of legal tools can be used to try and combat NCII, says Eric Goldman, a law professor at Santa Clara University. For example, victims can claim invasion of privacy. But using these tools isn’t particularly straightforward, and they may not even apply when it comes to someone’s body. If there aren’t, for instance, unique markers indicating that a body in a deepfake belongs to the person who says it does, US law “doesn’t really treat [this content] as invasion of privacy,” Goldman says, “because we don’t know who to attribute it to.”

In a 2018 study that reviewed “judicial resolution” of cases involving NCII, Goldman found that one successful way plaintiffs were able to win cases was to assert “intentional affliction of emotional distress.” But again, that hinges on the ability to clearly identify the person in the content. Relevant statutes, he adds, might also require “intent to harm the individual,” which may be hard to show for people whose bodies alone are featured.

“AI girls will do whatever you want”

In the last few years, Silverstein says, it’s become less and less common to see the bodies of real adult content creators in deepfakes, at least in a way that makes them clearly identifiable. 

Sometimes the bodies have been manipulated using AI or simpler editing tools. This can be as basic as erasing a birthmark or changing the size of a body part—minor edits that make it impossible to identify someone’s image beyond a reasonable doubt, so even porn actors who can tell that an altered image used their body as a base won’t get very far in the legal realm. “A lot of people are like, That looks like my body,” says Silverstein, but when he asks them how, they’ll reply, It just does

At the same time, other users are now creating NCII with wholly AI-generated bodies. In “nudify” apps, anyone with a minimal grasp of technology can upload a photo of someone’s clothed body and have it replaced with a fake naked one. “So [much] of this content being created is just someone’s face on an AI body,” Silverstein says.

Such apps have drawn a ton of attention recently, from Grok “nudifying” minors to Meta running ads for—and then suing—the nudify app Crushmate. But there’s been relatively little attention paid to the content being used to train them. They almost certainly draw on the more than 10,000 terabytes of online porn, and performers have virtually zero recourse. 

One reason is that creators aren’t able to demonstrate with any certainty that their content is being used to train AI models like those used by nudify apps. “These things are all a black box,” says Hany Farid, a professor at the University of California, Berkeley, who specializes in digital forensics. But “given the ubiquity” of adult content, he adds, it’s a “reasonable assumption” that online porn is being used in AI training. 

“It’s just not at all difficult to come up with pornographic data sets on the internet,” says Stephen Casper, a computer science PhD student at MIT who researches deepfakes. What’s more, he says, plenty of shadowy online communities provide “user guides” on how to use this data to train AI, and in particular programs that generate nudes. 

It’s not certain whether this activity falls within the US legal definition of “fair use”—an issue that’s currently being litigated in several lawsuits from other types of content creators—but Casper argues that even if it does, it’s ethically murky for porn created by consenting adults 10 years ago to wind up in those training data sets. When people “have their stuff used in a way that doesn’t respect or reflect reasonable expectations that they had at that time about what they were creating and how it would be used,” he says, there’s “a legitimate sense in which it’s kind of … nonconsensual.” 

Adult performers who started working years ago couldn’t possibly have consented to AI anything; Jennifer calls AI-related risks “retroactively placed.” Contracts that porn actors signed before AI, adds Silverstein, might provide that “the publisher could do anything with the content using technology that now exists or here and after will be discovered.” That felt more innocuous when producers were talking about the shift from VHS to DVD, because that didn’t change the content itself, just the way it was conveyed. It’s a far different prospect for someone to use your content to train a program to create new content … content that could replace your work altogether. 

Of course, this all affects creators’ bottom line—not unlike the way Google’s AI overviews affect revenue for online publishers who’ve stopped getting clicks when people are content with just reading AI-generated summaries. Performers’ “concern is … it’s another way to pirate [their] content,” says Rocket. 

After all, independent creators aren’t just “having sex on camera,” as the adult content creator Allie Eve Knox says. They’re paying for filming equipment and location rentals, and then spending hours editing and marketing. For someone to then rip off and distort that content “for their own entertainment or financial gain,” she says, “fucking sucks.” 

KIM HOECKELE

Tanya Tate, a longtime adult content creator, tells me about another highly unsettling AI-created situation: She was recently chatting with a fan on Mynx, a sexting app, when he asked her if she knew him. She told him no, and “his eyes just started watering,” Tate says. He was upset because he thought she did know him. Turns out he’d sent $20,000 to a scammer who’d used an AI-generated deepfake of Tate to seduce him. 

Several men, Tate subsequently learned, had been scammed by an AI version of her, and some of them began blaming her for their losses and posting false statements about her online. When she reported one particularly aggressive harasser to the police, they told her he was exercising his “freedom of speech,” she says. Rocket, too, is familiar with situations where AI is used to take advantage of fans. “The actual content creator will get nasty emails from these people who’ve been scammed,” she says.

Other porn actors say they fear that their likenesses have been used without consent to do other things they wouldn’t do. One, Octavia Red, tells me she doesn’t do anal scenes, “but I’m sure there’s tons of deepfake anal videos of me that I didn’t consent to.” That could cost her, she fears, if viewers choose to watch those videos instead of subscribing to her websites. And it could cause fans to develop false expectations about what kind of porn she’ll create.

“I saw one AI creator saying, ‘Well, AI girls will do whatever you want. They don’t say no,’” says Rocket. “That horrifies me … especially if they’re training those AI models on real people. I don’t think they understand the damage to mental health or reputation that that can create. And once it’s on the internet, it’s there forever.” 

Efforts to “scrub adult content from the internet”

As AI technology improves, it’s increasingly difficult for people to discern any type of real video from the best AI-generated ones on their own. In one 2025 study, UC Berkeley’s Farid found that participants correctly identified AI-generated voices about 60% of the time (not much better than random chance), while advances like false heartbeats make AI-generated humans tougher than ever to spot.

Nevertheless, most lawyers and legal experts I spoke with said copyright laws are still adult performers’ best bet in the US legal system, at least for getting their face-swapped content taken down. For his clients, Silverstein says, he tries to figure out the content’s origins and then issue takedown requests under the Digital Millennium Copyright Act, a 1998 law that adapted copyright law for the internet era. “Even recently, I had a performer who has an insanely well-known tattoo,” he says, and with a DMCA subpoena he managed to identify the poster of the content, who voluntarily removed it. 

But this way of working is becoming increasingly rare.

These days it’s nearly “impossible,” Silverstein says, to determine who produced a deepfake, because many platforms that host pirated content operate facelessly. They’re also often based in places that “don’t really care about US law when it comes to copyrights,” says Rocket—places like Russia, the Seychelles, and the Netherlands. 

While governments in the EU, the UK, and Australia have said they will ban or restrict access to nudify apps, it’s not an easily executed proposition. As Craanen notes, when app stores remove these services, they often simply reappear under different names, providing the same services. And social platforms where people share NCII deepfakes, argues Rocket, are slacking in getting them removed. “It’s endless, and it’s ridiculous, because places like Twitter and Facebook have the same technology we do,” Rocket says. “They can identify something as an infringement instantly, but they choose not to.”

(Apple spokesperson Adam Dema emailed, “’nudification’ apps are against our guidelines” in the app store, and it has “proactively rejected many of these apps and removed many others,” flagging a reporting portal for users. A Google spokesperson emailed, “Google Play does not allow apps that contain sexual content,” noting it takes “proactive steps to detect and remove apps with harmful content” and has suspended hundreds of apps for violating its policy. Meta spokesperson shared a blog post about actions it’s taken against nudify apps, but did not respond to follow-up questions about copyrighted material. X did not respond to a request for comment.)

As porn performers are forced to navigate AI-related threats, the only current federal law to address deepfakes may not help them much—and could even make matters worse. The Take It Down Act, which became US law last year, criminalizes publishing NCII and requires websites to remove it within 48 hours. But, as Farid notes, people could weaponize the measure by reporting porn that was made legally and with consent and claiming that it’s NCII. This could result in the content’s removal, which would hurt the performers who made it. Santa Clara’s Goldman points to Project 2025, the Heritage Foundation’s policy blueprint for the second Trump administration, which aims to wipe porn from the web. The Take It Down Act, he argues, “allows for the coordinated effort to scrub adult content from the internet.” 

US lawmakers have a history of hurting sex workers in their attempts to regulate explicit content online. State-level age verification laws are an example; visitors can pretty easily get around these measures, but they can still result in reduced revenue for adult performers (because of lower traffic to those sites and the high price of age-checking services they have to purchase). 

“They’re always doing something to fuck with the porn industry, but not in a way that actually helps sex workers,” says Jennifer. “If they do something, they’re taking away your income again—as opposed to something like giving you more rights to your image, [which] would be tremendously helpful.” 

But as generative AI plays an increasingly large role in NCII deepfakes, the types of images to which adult performers have rights moves deeper into a gray area. Can actors lay claim to AI images likely trained on their bodies? How about AI-generated videos that impersonate them, like the one that tricked Tanya Tate’s fan?

The biggest challenge will be creating “legitimate, effective laws that will absolutely protect content creators from abusing their likeness to train and create AI,” Rocket says. “Absent that, we’re just going to have to keep pulling content down from the internet that’s fake.”

In the meantime, a few porn actors tell me, they’re trying to take advantage of copyright laws that weren’t really made for them; they’ve signed with platforms that host their AI-generated duplicates, with whom fans pay to chat, in part so they’ll have contracts that protect ownership of their AI likenesses. When I spoke with the actor Kiki Daire in September 2025 for a story on adult creators’ “AI twins,” she said she “own[ed] her AI” because she’d signed a contract with Spicey AI, a site that hosted AI duplicates of adult performers. If another company or person created her AI-generated likeness, she added, “I have a leg to stand on, as far as being able to shut that down.”  

Even this, though, is not a sure thing; Spicey AI, for instance, shut down several months after I spoke with Daire, so it’s unlikely that her contract would hold. And when I spoke in October with Rachael Cavalli, another adult actor who had signed with an AI duplicate site in hopes it’d help protect her AI image, she admitted, “I don’t have time to sit around and look for companies that have used my image or turned something into a video that I didn’t actually do … it’s a lot of work.” In other words, having rights to your AI image on paper doesn’t make it easier to track down all the potentially infinite breaches of those rights online.

If she’d known what she knows about technology today, Jennifer says she doesn’t think she would have done porn. The risks have increased too much, and too unpredictably. She now does in-person sex work; it’s “not necessarily safer,” she says, “but it’s a different risk profile that I feel more equipped to manage.” 

Plus, she figures AI is unlikely to replace in-person sex workers the way it could porn actors: “I don’t think there’s going to be stripper robots.” 

Jessica Klein is a Philadelphia-based freelance journalist covering intimate partner violence, cryptocurrency, and other topics.

Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial

Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04386-7

As presented at the European Congress on Obesity, this randomized, placebo-controlled trial demonstrates that oral orforglipron, a nonpeptide GLP-1 receptor agonist, preserves weight loss and cardiometabolic benefits achieved with injectable GLP-1 receptor agonist therapies, making it a viable oral maintenance strategy.

Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial

Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04394-7

In a randomized trial, pasteurized Akkermansia muciniphila improved weight loss maintenance and metabolic health after a low-energy diet, especially in individuals with initially lower Akkermansia levels. The work suggests leveraging gut A. muciniphila as a potential target for weight management.

First Clinical Trial for a GLP-1 Gene Therapy Greenlit in Europe

Fractyl Health has received regulatory approval in the Netherlands to start the first-ever clinical trial for a gene therapy to treat type 2 diabetes. The upcoming Phase I/II clinical trial will test the safety and preliminary efficacy of RJVA-001, a gene therapy designed to locally deliver GLP-1 receptor agonist drugs with the goal of reducing the side effects associated with oral administration. 

“GLP-1 medicines have changed what is possible in obesity and type 2 diabetes, but they require chronic, high-dose systemic exposure that many patients cannot or do not sustain,” said Harith Rajagopalan, MD, PhD, co-founder and CEO of Fractyl Health. “RJVA-001 takes a different path: a potential one-time, pancreas-targeted gene therapy designed to enable the body to produce GLP-1 in response to meals: physiology, not pharmacology.” 

Based in Burlington, Massachusetts, Fractyl Health develops novel approaches to treating obesity and type 2 diabetes. The company’s lead program, an endoscopic procedure to maintain weight loss after discontinuing GLP-1 treatment for obesity, is currently being evaluated in a pivotal clinical trial. 

RJVA-001 leverages an engineered version of the human insulin promoter to trigger the production of GLP-1 in pancreatic beta cells when glucose levels rise after eating. The gene therapy is delivered using a minimally invasive endoscopic infusion directly into the pancreas, which is guided by ultrasound. 

The Phase I/II study will evaluate the safety, tolerability, and preliminary efficacy of three escalating doses of the gene therapy. Participants will include adults with type 2 diabetes who have previously responded well to oral GLP-1 treatment yet continue to experience difficulties controlling their blood sugar levels. 

“With this authorization, RJVA-001 becomes the first AAV gene therapy candidate to enter clinical development for type 2 diabetes,” said Rajagopalan. “We expect to dose the first patient and report initial data in the second half of 2026.”

Later this year, Fractyl expects to expand the study to additional sites in Australia, where the company has already submitted a clinical trial application and is currently awaiting a response from regulators. 

RJVA-001 will be the first candidate from Fractyl’s Rejuva platform to enter clinical development. This smart GLP-1 gene therapy platform focuses on the development of next-generation adeno-associated virus (AAV)-based gene therapies that are locally delivered to the pancreas. Another candidate developed through this platform includes a dual GIP/GLP-1 gene therapy to treat obesity, currently in preclinical development.  

“For decades, we have managed [type 2 diabetes] as a chronic, progressive disease that inevitably worsens over time. With this authorization, we are preparing to test, for the first time in humans, whether a one-time, pancreas-targeted gene therapy delivered via a routine endoscopic procedure could provide durable metabolic control by enabling physiologic, nutrient-responsive GLP-1 expression at the source of disease,” said Jacques Bergman, MD, PhD, professor of gastrointestinal endoscopy and deputy chair of the department of gastroenterology and hepatology at Amsterdam UMC, and a principal investigator of the upcoming clinical trial. 

“Patients who remain inadequately controlled despite maximally tolerated GLP-1 receptor agonists and multiple oral agents represent a population with significant unmet need. If successful, RJVA-001 could transform how we think about [type 2 diabetes], from a chronic disease you manage every day to one that could potentially be treated once.”

The post First Clinical Trial for a GLP-1 Gene Therapy Greenlit in Europe appeared first on Inside Precision Medicine.

STAT+: European Union inks a draft deal to boost local production of medicines and avoid shortages

The European Union reached a provisional deal to strengthen the supply of essential medicines — such as antibiotics, insulin, vaccines, and painkillers — and avoid shortages by ‌boosting domestic production and reducing reliance on imports.

Known as the Critical Medicines Act, the initiative seeks to avoid the kinds of withering drug shortages that were seen during the Covid-19 pandemic. Specifically, the proposal targets supply-chain weaknesses for more than 200 medicines that are considered critical ​to the region’s health security, including treatments for rare diseases.

“With today’s agreement, we are taking practical action to reduce our vulnerabilities, diversify supply chains and strengthen Europe’s capacity to produce critical medicines and their ingredients closer to home,” said Neophytos Charalambides, the health minister for Cyprus, in a statement.

Continue to STAT+ to read the full story…

Substance P–expressing neurons in the hypothalamic paraventricular nucleus mediate chronic cough hypersensitivity via the hypothalamus–airway neural pathway

Background and purposeIncreased cough sensitivity is the key pathophysiological mechanism of chronic cough. Although previous studies have focused on peripheral airway receptor sensitization, the role of the central nervous system—particularly the hypothalamic paraventricular nucleus (PVN)—remains unclear. Whether substance P (SP)–expressing PVN neurons contribute to cough hypersensitivity remains unknown.MethodsThree-week-old Hartley guinea pigs were divided into three groups: citric acid (CA), saline control (SA), and blank control (CON). A cough hypersensitivity model was induced by inhalation of 0.4 mol/L citric acid. Cough sensitivity was assessed using a capsaicin challenge, with the C5 threshold defined as the lowest capsaicin concentration inducing ≥5 coughs. Locomotor activity was evaluated using the open-field test. Airway inflammation and goblet cell hyperplasia were examined by HE and PAS staining. SP and c-Fos expression in the PVN were detected by immunofluorescence and Western blot. HSV retrograde tracing was used to analyze the PVN-airway neural pathway associated with cough hypersensitivity.ResultsCompared with the control groups, guinea pigs in the CA group exhibited a time-dependent increase in cough frequency and enhanced cough sensitivity, as indicated by a reduction in the C5 threshold. Histological analysis revealed increased inflammatory cell infiltration and goblet cell hyperplasia in the airways of the CA group. SP and c-Fos expression, along with the proportion of SP/Fos double-labeled neurons in the PVN, were significantly increased in the CA group (all P < 0.05). Viral tracing confirmed the presence of HSV-positive neurons in the PVN, supporting a neural connection between the PVN and the airways.ConclusionActivation of SP-expressing neurons in the PVN is associated with cough hypersensitivity and suggests the presence of a potential PVN–airway neural pathway. These findings provide a theoretical basis for the development of central-targeted therapies for chronic cough.