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Experimental Adjuvant Could Strengthen Mucosal Immunity with Injectable Polio Vaccines

The injectable form of the polio vaccine has proven effective at preventing illness but it does not block the transmission of the virus as well as the oral version of the vaccine. That is because the virus is usually transmitted through contaminated food or water and is first exposed to the GI tract, where the oral vaccine induces a mucosal immune response. To date, several countries no longer use the oral vaccine because there is a small risk of infection. It is also possible for people who receive the injected polio vaccine to spread the virus even though they are asymptomatic. 

Now according to data from an Massachusetts Institute of Technology-led study, it may be possible to modify the injectable vaccine so that it can also promote a mucosal immune response. This way, the vaccine could support polio eradication efforts without the risks of the oral polio vaccine. Details are published in a new Science Advances paper titled “Am80-Lipid nanoparticles serve as an enteric mucosal adjuvant 3 following parenteral immunization with inactivated polio vaccine.”

In comments that shed some light on the thinking behind the work, Ana Jaklenec, PhD, a principal investigator in MIT’s Koch Institute for Integrative Cancer Research, stated that while “people who are vaccinated with the injectable vaccine are not getting sick” they may be helping spread the highly contagious virus. “Mucosal immunity could help lower that shedding and ideally eliminate it,” she said. 

Her team’s version of the vaccine comprises an injectable, inactivated polio vaccine delivered with a nanoparticle-based adjuvant that helps steer immune cells to the mucosal lining of the intestine. Digging into the details, Jaklenec and her team worked with a group at Harvard Medical School who have shown previously that using a derivative of vitamin A as a vaccine adjuvant can help stimulate immune cells to go into the GI tract. 

Though the adjuvant, known as Am80, generates a strong response, one challenge is that it needs to be injected for several days in a row, which is not feasible for most vaccine campaigns. To eliminate the need for repeated vaccinations, the scientists used a lipid nanoparticle (LNP) as a delivery vehicle that releases the adjuvant slowly over several days.

Armed with the updated vaccine, the scientists moved on to testing it in rats. For their tests, the scientists injected the standard inactivated polio vaccine along with a separate injection of Am80 encapsulated in LNPs. They also delivered boosters to the rats at four and eight weeks. 

Following injection, LNPs accumulate in the lymph nodes where they interact with B and T cells that are also exposed to the polio vaccine. The interaction stimulates the cells to produce two surface proteins that direct them to the GI tract. Additionally, the B cells produce IgA antibodies, which protect body surfaces from infection by coating the mucosal membranes. Lastly the rats produce IgG antibodies in the bloodstream, which are similar to the antibodies produced in response to the standard injected polio vaccine. 

Overall, in the rats, they found that administering the vaccine and adjuvant produced a two-fold increase in the type of antibodies needed for mucosal immunity compared to the inactivated vaccine alone. Essentially, “by adding Am80 to lipid nanoparticle as an adjuvant, we are combining the safety of IPV with an adjuvant that can produce the mucosal immunity that normally you can only get with OPV,” said Behnaz Eshaghi, PhD, a postdoctoral student at MIT and lead author of the paper. 

For their next steps, the scientists plan to test the improved vaccine in other large animal models where they will inject the vaccine and adjuvant mixed together. More broadly, Am80 and similar adjuvants could help scientists design improved vaccines for other pathogens that infect the GI tract or for diseases that infect the lungs or reproductive tract. 

The post Experimental Adjuvant Could Strengthen Mucosal Immunity with Injectable Polio Vaccines appeared first on GEN – Genetic Engineering and Biotechnology News.

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Post-Stroke Arm Immobility Improved with Spinal Cord Stimulation

Stroke is the leading cause of arm and hand hemiparesis, weakness or paralysis on one side of the body, with about 80% of stroke patients experiencing at least partial weakness. Many stroke survivors rank improving arm function as a high priority for recovery, but effective treatments are not currently available.

Researchers at the University of Pittsburgh have just published the results of a pilot clinical trial to address this unmet need. Their work, which uses cervical spinal cord stimulation (SCS) to enhance arm and hand function was published in Nature Medicine.

“From a clinical perspective, even modest improvements in arm strength or control can make a meaningful difference in daily life of stroke survivors,” said study co-author George Wittenberg, MD, PhD, professor at the University of Pittsburgh School of Medicine.

This small pilot study included seven patients with varying levels of muscle hemiparesis caused by stroke. All patients presented with profound motor defects, with Fugl-Meyer Assessment (FMA) scores ranging from 15 to 35 (for context, the higher the score, the less impairment, with scores below 50 indicating severe impairment and scores over 100 indicating minimal to no impairment). Each patient was implanted with two leads implanted unilaterally in the cervical spinal cord and underwent SCS stimulation and worked on motor activity under researcher guidance over a four-week period.

During SCS testing, all patients experienced improvement in motor function with an average increase of 32% in strength and increase of 5.6 FMA points on average. After approximately 8.6 hours of motor activity (5.5 hours of which were with the SCS on), the FMA scores improved on average by 6.6 FMA points.

Researchers adjust spinal cord stimulation settings in real time to test their effects on arm and hand movement during stroke rehabilitation. [UPMC and University of Pittsburgh Health Sciences]

“This approach is designed to rapidly help people move their arms better, even years after a stroke,” said co-senior author Marco Capogrosso, PhD, assistant professor at the University of Pittsburgh and director of the spinal cord stimulation laboratory at Rehab Neural Engineering Labs in the UPMC Rehabilitation Institute.

“The stimulation works mostly as an assistive technology—when it’s on, people can move better,” Capogrosso continued. “By stimulating the spinal cord, we can immediately allow residual connections between the brain and the spinal cord to work more efficiently, enabling better movement.”

“Some of the improvements we measure may look small from the outside, but many stroke survivors are just on the verge of being able to do something important,” said Wittenberg. “Even a small change in motor function can be very significant if it helps someone button a shirt, open their hand or return to an activity they care about.”

While the patients in the study experienced immediate improvements to motor function, maintained improvement depended on continued use of SCS. Additional assessments showed motor function declined without continued stimulation, suggesting that the future use of SCS may not be with short-term use in rehabilitation but rather an assistive neuroprosthetic technology.

“This study represents the conclusion of our initial feasibility phase and an important step toward real-world clinical application,” Capogrosso said.

Based on the positive results from this pilot program, the researchers plan to expand the patient poll for a larger clinical trial to better understand the consequences of long-term SCS use, with and without physical therapy.

“Our goal is to develop a technology that could eventually be used in everyday life, not just in the clinic,” Capograsso concluded. “These results give us confidence that spinal cord stimulation could become a practical, implantable option for helping stroke survivors use their arms when it matters most.”

The post Post-Stroke Arm Immobility Improved with Spinal Cord Stimulation appeared first on Inside Precision Medicine.

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Infant Brain Development Sheds Light on Parkinson’s Link with Autism

Changes in the brains of babies shortly after birth could help explain why people go on to develop Parkinson’s disease (PD) and why this is particularly common in people with autism spectrum disorder (ASD).

The findings, in Science Advances, suggest a reason why humans are vulnerable to neurodegenerative diseases in a way that is not seen among other primates.

Researchers were surprised to find increased expression in genes associated with PD among humans that was not found in chimps or rhesus monkeys.

Human changes in regulatory DNA operated across two cell lineages, one linked with autism and the other with PD.

“Patients with ASD are also more likely to develop PD, a link that is currently not understood,” commented the researchers, led by Menno Creyghton, PhD, from Erasmus University Medical Center in the Netherlands.

“Our analysis linking the two diseases through a common network could provide insight into common biology between the two diseases.”

Human brains have several differences to those of primates, including a larger volume, more projections between outermost areas, and greater complexity of neurons in the upper layer.

The researchers note that, soon after birth, babies experience protracted brain development that coincides with periods of extensive synaptic modeling.

To investigate differences with our close evolutionary relatives, they conducted a single-cell transcriptomic and epigenomic analysis of human, rhesus macaque, and chimpanzee brain tissue during early postnatal development.

Through this, the team identified human infant–specific programs and cell states that were not observed in adults and correlated these early life processes with susceptibility to PD in aged neurons.

Specifically, Creyghton and co-workers identified human gene expression changes in immature oligodendrocytes enriched in both ASD risk genes and gene expression losses in patients with ASD.

There were also gene expression gains in human babies enriched in PD risk genes for and among genes dysregulated in PD patients.

Both transcriptional programs were part of a core network that contained human-specific sequence changes in regulatory DNA. This lacked cell lineage specificity, operating in both the oligodendrocyte and neuronal lineages, with different downstream targets for each.

In the oligodendrocyte lineage, the downstream target genes were overrepresented in autism risk genes whereas in the neural lineage, PD risk genes were enriched.

“It is therefore possible that these pathologies could be maintained in the human lineage by complex antagonistic interactions across developmental stages,” the authors speculated.

They noted the “unexpected” correlation between human evolution and Parkinson’s disease.

“It has been suggested that humans are exceptionally vulnerable to neurodegenerative diseases including PD as similar disease pathology has not clearly been observed in other primate species,” the team pointed out.

“We show that the human infant–specific expression changes that are overrepresented in PD-deregulated genes are enriched in synaptic developmental genes.

“Imbalances in synaptic function can strongly affect neural vulnerabilities, especially in larger projection neurons. As such, pathological deregulation of such a program may play a role in PD susceptibility.”

The post Infant Brain Development Sheds Light on Parkinson’s Link with Autism appeared first on Inside Precision Medicine.

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Alzheimer’s Genetic Risk Loci: 16 New Candidates

A comprehensive international genetics study found several new genetic risk factors for Alzheimer’s disease and related dementias, providing one of the clearest pictures of the biological pathways that cause the devastating neurodegenerative disorder.

Published in the journal Nature Genetics, the study combined data from 978,514 people of European ancestry, including over 128,681 individuals with Alzheimer’s disease and related dementias (ADRD). The researchers found 91 regions of the genome linked to dementia risk, including 16 new loci that had not been linked to Alzheimer’s in European populations.

The project brought together several major research consortia, including the European Alzheimer and Dementia Biobank, the International Genomics of Alzheimer’s Project, and the Psychiatric Genomics Consortium. By pooling results from 52 studies, scientists created one of the largest and most comprehensive genome-wide association analyses ever conducted for Alzheimer’s research.

Although aging is the strongest risk factor for Alzheimer’s disease, which affects tens of millions of people worldwide, genetics plays a major role in disease development. The APOE ε4 gene is known to strongly increase Alzheimer’s risk, but scientists believe many additional genes contribute smaller effects that together shape vulnerability.

The new study significantly expands that genetic map. Newly identified risk regions include genes involved in immune signaling, lipid metabolism, and cellular waste disposal—processes already suspected to contribute to the buildup of amyloid plaques and tau tangles, the hallmark pathologies of Alzheimer’s disease.

Several of the newly discovered loci, including SRC, PTPRC, MGAT5, and DOCK4, point toward the importance of microglia, the brain’s immune cells. Previous studies have suggested that dysfunctional immune responses may accelerate neurodegeneration by impairing the brain’s ability to clear toxic proteins.

Researchers also found evidence that many Alzheimer’s-associated genes are highly active in microglia across multiple brain regions, reinforcing the idea that inflammation and immune regulation are central to disease progression.

To distinguish true Alzheimer’s signals from broader dementia-related effects, the team performed additional analyses excluding “proxy” cases—individuals reporting a parent or sibling with dementia—and excluding large biobank datasets based primarily on medical coding. Even under these stricter conditions, 56 of the identified loci remained strongly associated with clinically diagnosed Alzheimer’s disease, suggesting the findings are robust.

Beyond identifying genes, the researchers tested how combined genetic risk influences brain pathology. They created polygenic risk scores using Alzheimer’s-associated variants other than APOE and examined their relationship to postmortem brain changes.

Individuals in the highest 10% of genetic risk had roughly double the likelihood of severe tau tangles and amyloid plaque buildup compared with people in the middle-risk group. Conversely, individuals in the lowest 10% had substantially reduced risk.

Importantly, the genetic scores were more strongly linked to classic Alzheimer’s pathology than to other forms of brain damage such as strokes or vascular disease. This suggests that many of the identified variants specifically contribute to Alzheimer’s biological mechanisms rather than dementia in general.

Despite the scale of the study, researchers caution that genetics alone cannot fully predict who will develop Alzheimer’s. The polygenic scores explained only a modest portion of disease variability, highlighting the continued importance of environmental and lifestyle factors.

Still, scientists say the findings could help accelerate the search for new drug targets and improve future risk prediction tools. The study also emphasizes the necessity of larger and more diverse datasets, as the current analysis focused primarily on individuals of European ancestry.

Future work will examine how rare genetic variants and structural changes in DNA contribute to Alzheimer’s biology, potentially paving the way to precision medicine and earlier intervention.

 

The post Alzheimer’s Genetic Risk Loci: 16 New Candidates appeared first on Inside Precision Medicine.

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STAT+: Supreme Court backs generic drugmaker in ‘skinny labeling’ case

The Supreme Court unanimously ruled that Hikma Pharmaceuticals did not infringe patents held by Amarin in a decision that makes generic drugmakers less vulnerable to lawsuits over so-called skinny labels.

The ruling overturned a lower court decision that sided with Amarin. Generic drugmakers had argued that, if the Supreme Court also ruled in favor of Amarin, they would be discouraged from making and selling lower-cost versions of brand-name medicines, which would maintain higher prices for prescription drugs.

At issue is skinny labeling, which refers to moves by generic companies that seek regulatory approval to market a medicine for a specific use, but not other patented uses for which a brand-name drug is prescribed. For instance, a generic drug could be marketed to treat one type of heart problem but not another. In doing so, the generic company seeks to avoid lawsuits claiming patent infringement.

Continue to STAT+ to read the full story…

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The Download: AI-generated lawsuits and virtual power plants for data centers

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

How courts are coping with a flood of AI-generated lawsuits

Most days in her chambers, Judge Maritza Braswell, a federal magistrate judge in Colorado, sifts through stacks of documents written by people without a lawyer. The number of these filings has more than doubled compared to before 2023. She puts that jump down to AI. 

But while AI appears to be expanding access to justice, it doesn’t seem to be improving people’s chances of winning. Judges are starting to question what rights and duties chatbots should have as they stand in for lawyers. Lawmakers, meanwhile, are grappling with who should pay the price when chatbots produce bad legal advice.

Read the full story on how AI is reshaping access to the law.

—Michelle Kim

How virtual power plants could provide energy for data centers

Would you take a payment to ramp down your electricity use? Would it change anything if you were doing so to help power a local data center? A new project backed by Google will put those questions to the test.

The company has signed a deal to fund a virtual power plant in the largest power grid in the US. The system will group together devices like electric vehicles and smart thermostats, paying customers to adjust their usage when the grid is stretched.

The project could free up capacity for Google’s data centers—but there’s a catch: people might not play along. Find out what the future holds for these virtual power plants.

—Casey Crownhart

This story is from The Spark, our weekly newsletter giving you the inside track on all things climate. Sign up to receive it in your inbox every Wednesday.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 The EU has proposed new legislation to end its Big Tech dependence
The laws aim to boost domestic ​cloud, AI and semiconductors. (CNBC)
+ US firms would be blocked from critical public tenders. (Reuters $)
+ It also wants to make sure non-EU actors cannot disrupt tech services with a “kill switch.” (The Guardian)
+ But the proposal needs to be negotiated with EU member states. (Politico $)

2 Intelligence agencies warn Chinese spies are recruiting on LinkedIn
The Five Eyes alliance said Beijing is using job platforms for espionage. (BBC)
+ The spies are allegedly recruiting government and military staff. (Politico $)
+ The Chinese embassy in the UK condemned the accusations. (Bloomberg $)
+ Meet the man hunting the spies in your smartphone. (MIT Technology Review)

3 AI CEOs have called for a law protecting against biological weapons
They warn that synthetic DNA could be used for bioweapons. (Wired $)
+ Sam Altman, Dario Amodei, and Demis Hassabis joined the call. (WSJ $)
+ No one’s sure if synthetic mirror life will kill us all. (MIT Technology Review)

4 Firms are using Reddit to manipulate ChatGPT and Google AI search
They’re spamming subreddits to get posts scraped by chatbots. (404 Media)
+ What we’ve been getting wrong about AI’s truth crisis. (MIT Technology Review)

5 Meta keeps delaying the launch of its new AI model
The new Muse Spark ‌AI model API still has no release date. (WSJ $)
+ Which is hampering Meta’s plans to monetize its AI investments. (Reuters $)

6 For the first time, a US city has voted to permanently ban data centers
Monterey Park, California, voted in favor of the move. (LA Times)
+ Should we be moving data centers to space? (MIT Technology Review)

7 China is betting on household chore training to advance robotics
Data harvested in homes and factories provides a scaling edge. (Rest of World)
+ Gig workers are training humanoids at home. (MIT Technology Review)

8 Sam Altman will urge US lawmakers not to require AI model approvals
He’s advocating against proposals for new AI rules. (Reuters $)
+ His move comes after President Trump signed a new AI order. (Wired $)

9 Quantinuum raised $1.68 billion in an IPO as quantum computing rises 
Investors flocked to one of the fast-growing sector’s leaders. (Reuters $)

10 Someone finally wants to hire philosophers: Silicon Valley
Big tech hopes they will help build better machines. (The Atlantic $)

Quote of the day

“Historically, these companies have been very willing to play Russian roulette—and they’re playing another round.”

—Connor Leahy, an AI researcher, former hacker and US director of ControlAI, tells the Financial Times why he’s concerned about Anthropic’s relentless race to the top.

One More Thing

Tentacle of Octopus

HENRY HORENSTEIN/GETTY


What an octopus’s mind can teach us about AI’s ultimate mystery

Emily Bender, a linguist at the University of Washington, has developed a thought experiment she calls the octopus test. It involves an octopus learning to copy patterns in human writing and produce squiggles in response. But does the animal actually understand the language or are we merely projecting meaning onto it?

Bender’s octopus is a stand-in for AI systems like ChatGPT. The intelligence we see in these machines is also projected on them by us. The same applies to consciousness: we may claim to see it, but it remains unclear whether it is really there.

Read the full story on the debate over machines with minds.

—Will Douglas Heaven

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ Discover where iconic sound effects actually came from in this fabulous audio history.
+ Need a serotonin boost? Then tune into this live puppy cam from Denali National Park.
+ Linux lovers can try 570 extinct operating systems at a new virtual museum.
+ Beethoven’s “Moonlight Sonata” becomes something entirely different in this lightning-fast bass guitar performance.