World’s smallest pacemaker is the size of a grain of rice

A dissolvable pacemaker that’s smaller than a grain of rice and powered by light could become an invaluable tool for saving the lives of newborn infants., The device can be implanted noninvasively via syringe, and may also be useful for adult patients dealing with certain heart defects. The medical breakthrough is detailed in a study published April 2 in Nature.

Roughly one percent of infants are born with heart defects every year. The majority of these cases only require a temporary implant for about seven days to allow time for the heart to naturally self-repair. But for low-resource regions of the world lacking access to advanced medical care, what should be a simple procedure can often end in tragedy. Meanwhile, the current standard for temporary pacemakers in adults also presents difficulties. Most procedures involve surgeons sewing electrodes directly onto the heart, then attaching those electrodes to an external pacing box using wires that exit a patient’s chest. Doctors remove the electrodes once they are no longer needed, but post-surgery risks include infection, damaged tissue, dislodgment, and blood clots. The wires sometimes also become encased in scar tissue, presenting further complications.

“That’s actually how Neil Armstrong died. He had a temporary pacemaker after a bypass surgery. When the wires were removed, he experienced internal bleeding,” experimental cardiologist and study co-lead Igor Efimov explained in a statement.

In 2021, a Northwestern University team including Efimov unveiled a quarter-sized, biodegradable temporary pacemaker without cumbersome batteries, rigid components, or wiring. The device relies on near-field communication protocols similar to those used in RFID tags and smartphones to complete electronic payments. For this to work, however, the pacemaker needed to include a built-in antenna to relay radio frequency commands.

“Our original pacemaker worked well. It was thin, flexible and fully resorbable. But the size of its receiver antenna limited our ability to miniaturize it,” said its co-creator and bioelectronics pioneer John Rogers.

Rogers, Efimov, and collaborators spent the next few years researching ways to shrink their temporary pacemaker to even smaller proportions. They eventually realized they could swap out the radio antenna for a design that instead relies on light-based data transmission. They also replaced the original device’s near-field communication power source with a galvanic cell—a type of battery that converts chemical energy into electrical energy. In the new version, the pacemaker relies on two metal electrodes that generate an electrical current after interacting with surrounding biofluids. This current is then directed to stimulate and regulate the heart through a miniscule, infrared light-activated switch installed on the battery’s opposite side.

“Infrared light penetrates very well through the body,” said Efimov. “If you put a flashlight against your palm, you will see the light glow through the other side of your hand. It turns out that our bodies are great conductors of light.”

Because the human heart requires only a small amount of electrical stimulation, researchers were able to shrink their next-generation pacemaker even smaller. The final result is a 1-millimeter-thick device measuring just 1.8 mm wide and 3.5 mm long that is still capable of delivering as much electrical stimulation as a standard pacemaker.

“We have developed what is, to our knowledge, the world’s smallest pacemaker,” Rogers said.

Given its materials safely dissolve over time, the pacemaker also doesn’t require any follow-up invasive surgery to remove it. This dramatically cuts down on the potential for post-op complications and trauma.

But why stop at just one miniature pacemaker? Efimov, Rogers, and collaborators believe that further advancements could allow the deployment of multiple devices across the heart. Once implanted, designers could coordinate them to move independently or together based on specific light wavelengths. This could lead to more complex synchronization therapies, including those that treat arrhythmias.

“We also could incorporate our pacemakers into other medical devices like heart valve replacements, which can cause heart block,” suggested Efimov.

The device’s size also means it can be incorporated into other implantable tools such as transcatheter aortic valve replacements, pain inhibitors, as well as nerve and bone restoration techniques. These future possibilities, however, all trace back to the team’s original goal.

“Our major motivation was children,” said Efimov. “Now, we can place this tiny pacemaker on a child’s heart and stimulate it with a soft, gentle, wearable device.”

Four potential side-effects of cholesterol-lowering drugs statins

In the early Noughties, “cholesterol” became a bit of a buzzword, with campaigns and advertisements telling us we should care about it – and seek to maintain healthy levels.

And although its prominence in conversation has died down somewhat in recent years, its importance is no less real, with 59% of people in the UK experiencing raised cholesterol in 2021. High levels of cholesterol was most evident in those aged 45 and 64 (72%) and among adults aged 16 to 33, men (53%) were more likely than women (46%) to have raised levels.

Now, a new study has also linked reduced levels of bad cholesterol with curbing the risk of dementia, finding that people with low-density lipoprotein (LDL-C) in their blood are 26% less likely to develop dementia and Alzheimer’s disease.

It also looked at the use of statins – cholesterol-lowering medications – and found them to provide an “additional protective effect” against the condition.

Here, we take a look at what statins are, how they work – and the potential side-effects and benefits of the drug.

A group of medicines that help lower the level of LDL cholesterol – “bad cholesterol” – in the blood, statins are designed to reduce the production of it inside the liver.

The drugs are normally prescribed to those with potentially dangerous levels of LDL-C, which, in turn, can lead to the hardening and narrowing of the arteries and result in cardiovascular disease or atherosclerosis.

Coming in tablet form, statins are taken once daily, but the dose will depend on your medical needs. This dosage may also change over time, depending on what your GP deems necessary.

Most people have to continue taking statins throughout their life once they have been prescribed them.

  • Headaches
  • Dizziness
  • Nausea
  • Digestive problems, such as indigestion, diarrhoea or constipation
  • Muscle pain
  • Problems with sleep
  • Low blood platelet count
  • Feeling tired or physically weak
  • Muscle damage – This usually only happens when statins are taken in combination with other medication
  • Loss of sensation or tingling in the nerve endings
  • Tendon problems
  • Hair loss
  • Memory problems
  • Skins irritation
  • Loss of sex drive
  • Erectile dysfunction
  • Being sick
  • Liver damage

 

In addition to the 2025 study published in the Journal of Neurology, Neurosurgery & Psychiatry (outlined above), a 2016 study published by the same journal also linked statins to a lower risk of dementia and Alzheimer’s.

Looking at 400,000 Medicare beneficiaries who used the drugs, the research found that men in the group who had taken the medication regularly for two years had a 12% lower risk of developing Alzheimer’s.

Various studies have also looked at the impact statins have on cancer risks, but the results have been inconsistent and there’s no conclusive answer right now. More research needs to be done to gauge whether statins can, indeed, lower the risk of certain cancers.

The drugs have also been found to reduce inflammation and irritation, and the exacerbation of atherosclerosis, which is a major cause of coronary artery disease (CAD).

Research published by Nature Communications in 2019 discovered a new link between statins and immune systems. It found that by using medications like statins, they could modify cell responses in the lab. Professor Andrew Cope, lead investigator of the study, said: “We think that our findings could explain why people taking statins are better at fighting influenza, and why patients have better outcomes for some types of cancer.”

Shingles Vaccine May Protect Against Dementia Risk

A newly reported study by a Stanford Medicine-led team has provided what the researchers suggest is the strongest evidence yet that a vaccine can reduce the risk of dementia. Taking advantage of a particular public health policy in Wales that means eligibility for the shingles (herpes zoster) vaccine is based on an individual’s exact date of birth, the team analyzed the health records of older adults, discovering that those who received the live attenuated vaccine were 20% less likely to develop dementia over the next seven years than those who did not receive the vaccine.

The findings, published in Nature, support an emerging theory that viruses that affect the nervous system can increase the risk of dementia. In their paper (“A natural experiment on the effect of herpes zoster vaccination on dementia,”) research lead and senior author Pascal Geldsetzer, MD, PhD, assistant professor of medicine, and colleagues, concluded, “Our substantial effect sizes, combined with the relatively low cost of the zoster vaccine, imply that, if these findings are truly causal, the zoster vaccine will be both far more effective as well as cost-effective in preventing or delaying dementia than existing pharmaceutical interventions.”

Shingles, a viral infection that produces a painful rash, is caused by the same virus—varicella zoster virus (VZV)—that causes chicken pox. After people contract chicken pox, usually in childhood, the virus stays dormant in the nerve cells for life. In people who are older or have weakened immune systems, the dormant virus can reactivate and cause shingles.

Dementia affects more than 55 million people worldwide, with an estimated 10 million new cases every year. Decades of dementia research have largely focused on the accumulation of plaques and tangles in the brains of people with Alzheimer’s, the most common form of dementia. But a lack of breakthroughs in prevention or treatment is leading some researchers to explore other avenues, including the role of certain viral infections.

In their newly released Nature paper, Geldsetzer and colleagues pointed out, “Recently, evidence has grown that neurotropic herpesviruses may have a role in the pathogenesis of dementia. One approach to targeting herpesviruses is vaccination.” However the team continued, vaccines are increasingly being recognized as eliciting a broader immune response that can have important off-target effects. To date, they continued, “… studies in cohort and electronic health record data on the effect of vaccination receipt on dementia have simply compared the occurrence of dementia among those who received a given vaccination and those who did not.”

Such studies have to assume that characteristics that are different between vaccinated and unvaccinated individuals—and that are also related to dementia—have been sufficiently well measured and modeled so that there are no remaining factors that might confound any relationship between vaccination receipt and dementia. But, as the team commented, “This assumption of no confounding bias is often implausible because it has to be assumed that the study has detailed data on factors that are difficult to measure, such as personal motivation or health literacy.”

So, while previous studies based on health records have linked the shingles vaccine with lower dementia rates, they could not account for a major source of bias, in that people who are vaccinated also tend to be more health conscious in many difficult-to-measure ways. Behaviors such as diet and exercise, for example, are known to influence dementia rates, but are not included in health records.

“All these associational studies suffer from the basic problem that people who get vaccinated have different health behaviors than those who don’t,” said Geldsetzer. “In general, they’re seen as not being solid enough evidence to make any recommendations on.”

Two years ago Geldsetzer recognized a fortuitous “natural experiment” in the rollout of the shingles vaccine in Wales that offered a potential way to deal with this bias. “To provide causal as opposed to correlational evidence, we take advantage of the fact that, in Wales, eligibility for the zoster vaccine was determined on the basis of an individual’s exact date of birth,” the investigators explained. The vaccine being used at that time contained a live-attenuated, or weakened, form of the virus.

The vaccination program, which began Sept. 1, 2013, specified that anyone who was 79 on that date was eligible for the vaccine for one year. (People who were 78 would become eligible the next year for one year, and so on.) People who were 80 or older on Sept. 1, 2013, were out of luck—they would never become eligible for the vaccine. The authors summarized, “Those born before 2 September 1933 were ineligible and remained ineligible for life, whereas those born on or after 2 September 1933 were eligible for at least one year to receive the vaccine.”

These rules, designed to ration the limited supply of the vaccine, also meant that the slight difference in age between 79- and 80-year-olds made all the difference in who had access to the vaccine. By comparing people who turned 80 just before Sept. 1, 2013, with people who turned 80 just after, the researchers could isolate the effect of being eligible for the vaccine.

The circumstances, well-documented in the country’s health records, were about as close to a randomized controlled trial as you could get without conducting one, Geldsetzer pointed out. “Importantly, individuals who are only a few weeks apart in age are not expected to differ systematically from each other,” the authors commented. “That is, all potential confounding variables are in expectation balanced between our comparison groups.” By taking advantage of what they described as “this unique natural experiment” the scientists could avoid confounding “more credibly” than other studies that had compared vaccine recipients to non-recipients while trying to control for “the myriad of differences” between the groups.

For their reported study, Geldsetzer and colleagues looked at the health records of more than 280,000 older adults who were 71 to 88 years old and did not have dementia at the start of the vaccination program. They focused their analysis on those closest to either side of the eligibility threshold—comparing people who turned 80 in the week before the cutoff with those who turned 80 in the week after. “We know that if you take a thousand people at random born in one week and a thousand people at random born a week later, there shouldn’t be anything different about them on average,” Geldsetzer said. “They are similar to each other apart from this tiny difference in age.”

The same proportion of both groups likely would have wanted to get the vaccine, but only half, those almost 80, were allowed to by the eligibility rules. “What makes the study so powerful is that it’s essentially like a randomized trial with a control group—those a little bit too old to be eligible for the vaccine—and an intervention group—those just young enough to be eligible,” Geldsetzer added.

Over the next seven years, the researchers compared the health outcomes of people closest in age who were eligible and ineligible to receive the vaccine. By factoring in actual vaccination rates—about half of the population who were eligible received the vaccine, compared with almost none of the people who were ineligible—they could derive the effects of receiving the vaccine.

They found that, as expected, the vaccine reduced the occurrence over that seven-year period of shingles by about 37% for people who received the vaccine, similar to what had been found in clinical trials of the vaccine. (The live-attenuated vaccine’s effectiveness wanes over time.)

By 2020, one in eight older adults, who were by then 86 and 87 years of age, had been diagnosed with dementia. But those who received the shingles vaccine were 20% less likely to develop dementia than those who were unvaccinated. “Scaled to account for the fact that not all those who were eligible received the vaccine, we find that actually receiving the zoster vaccine reduced the probability of a new dementia diagnosis by 3.5 (95% CI = 0.6–7.1; P = 0.019) percentage points, corresponding to a relative reduction of 20.0%,” the team wrote. “It was a really striking finding,” Geldsetzer said. “This huge protective signal was there, any which way you looked at the data.”

The scientists searched high and low for other variables that might have influenced dementia risk but found the two groups to be indistinguishable in all characteristics. There was no difference in the level of education between the people who were eligible and ineligible, for example. Those who were eligible were not more likely to get other vaccinations or preventive treatments, nor were they less likely to be diagnosed with other common health conditions, such as diabetes, heart disease, and cancer. “… we have provided evidence from a series of analyses against any of the possible remaining sources of bias being a likely explanation of our findings,” the authors stated.

The only difference was the drop in dementia diagnoses. “Because of the unique way in which the vaccine was rolled out, bias in the analysis is much less likely than would usually be the case,” Geldsetzer said. The team further noted, “By taking advantage of the fact that the unique way in which the zoster vaccine was rolled out in Wales constitutes a natural experiment, and examining each possible remaining source of bias, our study provides evidence that is more likely to be causal in nature than the existing, exclusively associational, evidence on this topic.”

The team did still analyze the data in alternate ways—using different age ranges or looking only at deaths attributed to dementia, for example—but the link between vaccination and lower dementia rates remained. “The signal in our data was so strong, so clear and so persistent,” Geldsetzer said.

In a further finding, the study showed that protection against dementia was much more pronounced in women than in men. “We observed large differences in the effect of zoster vaccination on dementia between women and men, with women benefitting more than men,” the investigators wrote. This could be due to sex differences in immune response or in the way dementia develops, Geldsetzer suggested. Women on average have higher antibody responses to vaccination, for example, and shingles is more common in women than in men.

Whether the vaccine protects against dementia by revving up the immune system overall, by specifically reducing reactivations of the virus or by some other mechanism is still unknown. Also unknown is whether a newer version of the vaccine, which contains only certain proteins from the virus and is more effective at preventing shingles, may have a similar or even greater impact on dementia. “… because the newer recombinant subunit zoster vaccine (Shingrix) replaced the live-attenuated zoster vaccine (Zostavax) in the United Kingdom only in September 2023, which is after our follow-up period ended, our effect estimates apply to the live-attenuated zoster vaccine only,” the authors stated.

Geldsetzer hopes the new findings will inspire more funding for this line of research. “Other than investing into randomized trials, investments into basic science research on the potential role of VZV and the immune response to the zoster vaccine in the pathogenesis of dementia could provide critical mechanistic insights,” the authors further noted. “At least investing a subset of our resources into investigating these pathways could lead to breakthroughs in terms of treatment and prevention,” Geldsetzer added.

In the past two years, his team has replicated the Wales findings in health records from other countries, including England, Australia, New Zealand, and Canada, that had similar rollouts of the vaccine. “We just keep seeing this strong protective signal for dementia in dataset after dataset,” he said. Geldsetzer has set his sights on a large, randomized controlled trial, which would provide the strongest proof of cause and effect. Participants would be randomly assigned to receive the live-attenuated vaccine or a placebo shot. “It would be a very simple, pragmatic trial because we have a one-off intervention that we know is safe,” he noted.

Geldsetzer is seeking philanthropic funding for the trial as the live-attenuated vaccine is no longer manufactured by pharmaceutical companies. And such a trial might not take long to see results. A graph of the Wales data tracking the dementia rates of those who were eligible and ineligible for the vaccine shows the two curves began to separate in about a year and a half.

In a related News & Views, Anupam B. Jena, MD, PhD, at the Department of Health Care Policy at Harvard Medical School and the Department of Medicine, Massachusetts General Hospital, commented that while it’s not yet clear exactly how herpes zoster vaccination lowers the risk of dementia, the reported study has profound implications. “The vaccine could represent a cost-effective intervention that has public-health benefits strongly exceeding its intended purpose,” Jena stated. “Given the substantial economic and social burden of dementia, policymakers and healthcare providers might need to reassess the value of widespread herpes zoster vaccination, particularly in older adults.”

AIRNA Closes $155M Series B Round to Fund ATTD Trial, Build Pipeline

RNA editing therapy developer AIRNA has closed on an oversubscribed $155 million Series B financing it said will help it advance its lead program targeting Alpha-1 antitrypsin deficiency (AATD) into a Phase I/II trial this year.

The financing comes less than a year after AIRNA completed a $90 million Series A, of which $60 million was raised just last summer, and at a time when many other startups have struggled to raise venture capital. While president and CEO Kris Elverum said he can’t speak to the broader challenges of early-stage companies pursuing capital, he told GEN Edge that AIRNA’s success with investors reflected their alignment with the company’s three-prong approach to RNA drug development.

“The first is that RNA editing is clearly going to be a breakthrough modality that will deliver multiple medicines to help patients,” Elverum said. “We’re using multiple proven components from other [RNA] modalities—in particular siRNA—to enable optimal potency at lower doses with safe, infrequent, subcutaneous administration.”

The second, he continued, is AIRNA’s effort to develop a best-in-class AATD treatment that will deliver optimal potency at lower doses with safe, infrequent, subcutaneous administration. The third, Elverum added, is AIRNA’s commitment to building a top-tier pipeline.

“AIRNA stands alone in pursuing the introduction of healthy variants to address common diseases with RNA editing. And we’re really excited about the future for what we were going to be able to do across multiple different diseases to help people,” Elverum said.

AIR-001 is designed to restore functional alpha-1 antitrypsin (M-AAT) protein production by precisely repairing the SERPINA1 mutation (PiZ) to address the underlying cause of both lung and liver disease. According to AIRNA, AIR-001 offers potent and durable M-AAT production, convenient, subcutaneous dosing, and well-tolerated safety.

Growing field targets AATD

By focusing on AATD, AIRNA joins a growing field of drug developers targeting the genetic condition. Furthest along is Wave Life Sciences, whose AATD candidate WVE-006 succeeded last October in the first-ever clinical demonstration of RNA editing in humans by achieving positive proof-of-mechanism in an early-phase clinical trial.

Later this year, Wave expects to present additional data from its Phase Ib/IIa RestorAATion-2 trial (NCT06405633) assessing the effect of multiple doses and a higher dose level of WVE-006, on the production of healthy, wild-type, M-AAT protein, and potentially the effect of extended dose intervals. In March, Wave said multi-dosing of patients was ongoing in the trial’s 200 mg cohort, while a second single dose cohort of 400 mg has been launched.

Also pursuing an AATD therapy is Beam Therapeutics, which won FDA clearance for its investigational new drug (IND) application to expand into the United States its ongoing Phase I/II trial (NCT06389877) of BEAM-302, an in vivo liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents. BEAM-302 is designed to treat AATD by correcting the disease-causing PiZ mutation.

Earlier in March, Beam announced positive initial safety and efficacy data from the trial: a single infusion of BEAM-302 led to rapid, durable, and dose-dependent increases in total AAT across all three dosages studied (20 mg, 40 mg, and 60 mg), as well as new production of corrected protein (M-AAT) and decreases in mutant AAT (Z-AAT). At the high 60 mg dosage, total AAT at day 28 nearly tripled from 4.4 to 12.4 µM, above the 11 µM protective threshold. Beam said the data established clinical proof-of-concept for BEAM-302 as a potential treatment for AATD, as well as for in vivo base editing.

On March 18, Prime Medicine unveiled a preclinical prime editing program designed to treat AATD by using a universal liver lipid nanoparticle (LNP) to edit the PiZ mutation (also known as Pi*Z or E342K) in SERPINA1. Prime said LNP delivery of its Prime Editors showed up to 72% precise correction of the SERPINA1 gene in the hepatocytes of fully humanized mice, restoring over 95% of serum AAT to the corrected isoform, with healthy M-AAT protein in the serum at levels “well above” 20 µM.

A developer of CRISPR-based gene editing therapies, Intellia Therapeutics, ended development in January of its AATD candidate NTLA-3001 as part of a cost-cutting restructuring that included the planned elimination of 27% of its workforce during 2025. That would translate to approximately 110 jobs, based on the workforce total of 403 full-time employees as of February 14 disclosed by Intellia in its Form 10-K annual report.

Functional cure

“I think it’s more important to be best for patients than it is to be first in patients, and the unique opportunity that we have for patients with AATD is to bring them a functional cure that is a very potent repair of the mutation that’s causing their disease,” Elverum said.

“That repair allows for high levels of M-AAT protein to be produced, which is what’s really important for lung function, but to do so at low doses that can be safe and infrequently administered subcutaneously and allow patients to maintain control and freedom over their healthcare choices over the long term,” he added.

AIRNA’s AIR-001 leads a pipeline about which the company has not disclosed many details. Elverum said AIRNA’s therapeutic areas of interest include cardiometabolic disease, where its sole disclosed program entails introducing an as-yet undisclosed beneficial variant in vivo. It’s a similar mechanism to a program in AIRNA’s revealed pipeline for an undisclosed therapeutic area.

Elverum won’t say whether AIRNA’s focus on cardiometabolic disorders will include developing alternatives to glucagon-like peptide 1 (GLP-1) therapies. GLP-1s indicated for obesity and diabetes have grown into blockbuster drugs generating billions of dollars in sales for leading companies Novo Nordisk and Eli Lilly—but which have been linked in studies to side effects ranging from sagging facial skin (“Ozempic face”) to loss of muscle mass.

AIRNA develops therapies based on its RESTORE+™ RNA editing platform. RESTORE+ first targets a defined site in the RNA strand, activating changes to composition and functionality of a therapeutically relevant protein. The platform optimizes the chemistry, sequence, and delivery of oligos that precisely engage the RNA at the target site upon delivery into the cell, with the goal of enabling precise, efficient, and safe RNA editing.

Following target engagement, the oligo recruits endogenous adenosine deaminases acting on RNA (ADAR) to make an adenosine-to-inosine (A-to-I) edit at the target site that is read as guanosine (G). The A-to-I edit changes the code in the RNA, enabling the repair of pathogenic point mutations, or inducing therapeutically effective gain or loss-of-function mutations that precisely change protein activity.

Growth plan

With operations divided between its home base in Cambridge, MA, and Tübingen, Germany, where the company oversees a research hub, AIRNA foresees growth to its staff of over 50 people this year.

“Our growth is really going to be focused on that next stage of our development as we are bringing our medicines to patients. You can think about the medical function, the manufacturing function, and the like. That is going to be key for us as we move forward,” Elverum said.

The Series B round brings AIRNA to $245 million in total capital raised, and comes less than a year after AIRNA closed on $60 million in financing that was also oversubscribed—and brought the value of the company’s Series A to $90 million. AIRNA emerged from stealth in September 2023 with its first $30 million in initial financing from an investor syndicate led by ARCH Venture Partners.

Venrock Healthcare Capital Partners led the Series B financing, with Forbion Growth serving as co-leader. Participants in the Series B included RTW Investments, Nextech Invest, ARCH Venture Partners, Forbion Ventures, ND Capital, and other undisclosed new and existing investors.

In connection with the latest financing, Melissa McCracken, PhD, a partner at Nextech Invest, has been appointed to AIRNA’s board.

“AIRNA’s innovative approach to RNA editing has the distinctive potential to improve health across large populations by introducing healthy genetic variants for many conditions,” stated Dirk Kersten, managing partner at Forbion. “We are excited to support the expansion of AIRNA’s pipeline of life-changing medicines and the advancement AIR-001 into the clinic.”

SAMBAI Selects Akoya’s PhenoCycler-Fusion Spatial Proteomics Technology for Large-Scale Cancer Study

SAMBAI, a team funded through the Cancer Grand Challenges initiative, reported that Akoya Biosciences’ PhenoCycler®-Fusion system will be the foundational spatial proteomics technology used to generate data for a biobank and data repository for cancer equity research.

SAMBAI, which stands for “Societal, Ancestry, Molecular and Biological Analyses of Inequalities,” explained that the objective is to understand the mechanisms and contributions of genetics, biology, environmental, and social determinants to cancer risk and outcomes in diverse populations, and to provide foundational knowledge for developing novel approaches to reduce cancer inequities.

SAMBAI will receive up to $25 million from Cancer Grand Challenges to develop the project and focus on assessing disparate cancer outcomes in 40,000 individuals of African descent from Africa, the U.K., and the U.S., and include proteomics, transcriptomics, and other data types.

Teams from Johns Hopkins University, Nottingham University, Glasgow University, and King’s College London will run thousands of samples on the PhenoCycler-Fusion system using panels designed to study breast, pancreatic, and prostate cancers. These three cancers have a disproportionately higher rate of aggressive tumor grade and early onset in the target population.

“We are excited that the PhenoCycler-Fusion is the spatial proteomics technology of choice for analyzing thousands of patient samples as part of this important initiative,” said Brian McKelligon, CEO of Akoya Biosciences. “A study of this size demands the high plex and high throughput of our solutions to generate data at the scale needed. We are honored to play a role in defining the factors that influence disparate outcomes in underserved populations.”

Akoya’s technology is well suited to assess the effect of environmental and societal factors on biology at the molecular level and on the development of cancer at the scale required for this project, according to Melissa Davis, PhD, director of the Institute of Translational Genomic Medicine at Morehouse School of Medicine and leader of team SAMBAI.

“For the first time in a large population, we plan to bring all of these factors together to understand their interconnectedness and contribution to disparities in health outcomes,” she explained.

Inhibiting FGFR2 Supports Prevention and Delay of Common Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent type of pancreatic cancer, characterized as a highly lethal malignancy that is often preceded by precancerous lesions. These lesions are relatively common, but only a small portion will progress to PDAC.

In a new study published in Cancer Research titled, “FGFR2 Abrogation Intercepts Pancreatic Ductal Adenocarcinoma Development,” researchers from Cold Spring Harbor Laboratory (CSHL) have identified a new mechanism to delay KRAS-mutated PDAC development in mice. While KRAS mutations are one of the most common oncogenes, standard targeted therapies leveraging KRAS inhibitors have seen limited success.

Led by David Tuveson, PhD, the Roy J. Zuckerberg professor of cancer research and cancer center director at CSHL, the research team analyzed murine and human pancreatic tissue specimens, and found that fibroblast growth factor receptor 2 (FGFR2) expression, a protein that plays a crucial role in cell growth, differentiation, and bone development, was higher in KRAS-mutated precancerous lesions and some KRAS-mutated PDAC, compared with normal tissue. Notably, FGFR2 expression in murine precancerous lesions correlated with an increase in mutant KRAS signaling.

Results showed that FGFR2 gene deletion led to significantly fewer precancerous lesions and delayed PDAC tumor formation compared with mice with an intact FGFR2 gene. In addition, the combined inhibition of FGFR2 and another signaling protein, EGFR, significantly reduced the formation of precancerous lesions in mice carrying mutated KRAS.

“We know that precancerous pancreatic lesions often carry KRAS mutations,” said Claudia Tonelli, PhD, lead author of the study and research investigator at CSHL. “Our observation that FGFR2 expression was associated with increased KRAS signaling suggests that FGFR2 may play a key role in driving the progression of KRAS-mutated precancerous lesions to malignancy,” said Tonelli.

Tonelli also noted that while mutations in the KRAS protein are known to drive pancreatic cancer, they do not appear to be sufficient to promote the transition from precancerous lesions to cancer.  

“Understanding the additional pathways that promote progression from a precancerous pancreatic lesion to a malignant tumor could help identify more viable treatment strategies as well as cancer interception approaches to stop PDAC from developing in the first place,” Tonelli said. 

The findings suggest that targeting FGFR2 could potentially benefit patients at high risk of their precancerous lesions progressing to PDAC. While FGFR inhibitors are clinically available, Tonelli cautioned that their effectiveness in intercepting PDAC would first need to be tested in clinical trials before they could be used for this purpose. 

“Our study provides critical insights into pancreatic cancer development and could guide the development of strategies for the interception and prevention of pancreatic malignancies,” she said. 

Additional projects in Tuveson’s cancer research lab explore changes in redox metabolism associated with pancreatic cancer tumorigenesis, dissect signaling by the Ras oncogene, discover new biomarkers of early pancreas cancer, and identify mechanisms of crosstalk between pancreatic cancer cells and the tumor stroma. 

To dissect molecular changes associated with pancreatic tumorigenesis, the Tuveson lab has generated a large collection of human patient-derived organoid models. By measuring the therapeutic sensitivities of patient-derived organoids, the lab is working to identify novel strategies to treat patients as well as markers of therapeutic response. 

Edible biofilm based on pomegranate peel extract extends the shelf life of strawberries

An edible biofilm, obtained from agricultural and fishing waste and developed by researchers at the São Carlos Institute of Chemistry of the University of São Paulo (IQSC-USP) in Brazil, allows the shelf life of strawberries (Fragaria x ananassa Duch.) to be extended.

In laboratory tests, the researchers found that over 12 days of refrigerated storage, the fruit coated with the film lost 11% weight and took between 6 and 8 days to start becoming contaminated with fungi, compared to 4 days for fruit not covered with the material.

The results of the work, carried out in collaboration with researchers from EMBRAPA Instrumentation and the Federal University of São Carlos (UFSCar), are published in the journal Food Chemistry.

“By applying the coating, it was possible to double the shelf life of strawberries kept under refrigeration and delay the dehydration of the fruit, while preserving the taste, texture and volatile compounds that give the fruit its characteristic aroma,” Mirella Romanelli Vicente Bertolo, first author of the study and a postdoctoral researcher at EMBRAPA Instrumentation, says.

The work began during Bertolo’s doctoral studies at IQSC-USP under the supervision of Professor Stanislau Bogusz Junior. During their research, they developed a technique that allowed them to extract 84.2% more antioxidants—substances with preservative properties—from the peel of pomegranate (Punica granatum L.) using natural deep eutectic solvents (NADES).

“More than 40% of the pomegranate, depending on the variety, is made up of peel, which is wasted. Our idea was to use this waste to obtain extracts rich in phenolic compounds with antioxidant and antimicrobial activities,” says Bogusz.

With the success of developing the extraction method, the researchers decided to test the hypothesis of incorporating the antioxidants in pomegranate into coatings based on gelatin and chitosan—a polymer (natural polysaccharide) found in the skeletons of crustaceans such as shrimp—to develop a protective film for fruit.

“We chose to use chitosan extracted from squid glia [inner shells] through a process of deacetylation of the chitin found in this mollusk, because it doesn’t have the problem of allergenicity like that obtained from shrimp. And we combined this material with another polymer, in this case gelatin, to improve its mechanical properties,” explains Bogusz.

Highly perishable fruit

The strawberry was chosen as a model system to test the effectiveness of the biofilm because it is one of the items with the highest loss rates in Brazilian supermarkets due to its perishability and short shelf life of about less than seven days under refrigeration.

“The strawberry is a fruit that has very high respiratory activity and a very low pH [acidity]. It’s therefore very susceptible to microbial attack. It’s also very moist and the fruit is small. Based on this, we hypothesized that if the material we developed worked, it’d be effective on any other fruit,” says Bogusz.

To test this hypothesis, the researchers coated strawberries with the edible film by immersion and evaluated the effects of the material on the physicochemical, microbiological and volatile profile and sensory characteristics of the fruit over 12 days of refrigerated storage.

The results indicate that the material forms a film on the surface of the fruit that acts as a barrier to the passage of microorganisms, moisture loss and gas exchange, modifying the strawberry’s respiration. In this way, the coating slows down the metabolism of the fruit during the post-harvest period, thereby increasing its shelf life and preserving the color, firmness and bioactive compounds of the fruit.

“We found that the film made it possible to maintain the texture, delay contamination by microorganisms and reduce the loss of fruit mass, which is observed when the strawberry shrivels. This happens very often with uncoated fruit because it easily loses water and dehydrates,” says Bertolo.

According to the researcher, the film also made it possible to reduce the severity of fungal damage and improve the volatile profile of the fruit. “The material made it possible to preserve 40% more of the compounds responsible for the fruit’s aroma,” says Bertolo.

The biofilm also didn’t interfere with the sensory characteristics of the fruit, such as flavor, as confirmed by sensory analysis tests conducted with undergraduate chemistry students at IQSC-USP.

“The results of the tests showed that there were no differences in the taste, aroma or visual characteristics of strawberries coated with the material compared to strawberries without the film,” says Bertolo.

The researchers have filed a patent application for the formulation and intend to license the technology to interested companies.

Economic analyses indicate that the coating could cost an estimated BRL 0.15 per fruit.

“This is a cost that consumers may be willing to pay for fruit with a longer shelf life and greater usage,” Bertolo estimates.

Screen time in bed linked to worse sleep, study finds

People who spend more time looking at a screen in bed are more likely to report insomnia and sleep loss, a study has found.

The research is based on a Norwegian survey of more than 45,000 students.

It indicates that each additional hour of screen time was linked to a 63% increase in insomnia risk, and 24 minutes less sleep.

However, the researchers said they had only established a correlation between screen use and lower sleep quality and had not demonstrated that the former caused the latter.

Experts say putting down your phone before bed, doing something relaxing and establishing a routine may help improve sleep.

The researchers behind the study, based on nationally representative survey data of 18-28 year old students gathered in 2022, wanted to examine the link between the amount of time spent using screens in bed and sleep patterns.

They also sought to probe the impact on sleep of using social media compared to other screen activities.

Dr Gunnhild Johnsen Hjetland of the Norwegian Institute of Public Health, who is lead author of the research – which was published in a Frontiers journal – said the type of screen activity appeared to be less impactful than screen time on the whole.

“We found no significant differences between social media and other screen activities, suggesting that screen use itself is the key factor in sleep disruption,” he said.

Sleep or social media

The 2022 Norway health and wellbeing survey asked participants to identify if they used any digital media after they had gone to bed.

Options included watching films or TV, checking social media, browsing the internet and gaming.

Among those saying they used screens in bed before sleep, 69% said they used social media as well as other screen-based activities.

Participants were also asked to identify how many nights a week they would engage with such media, and for how much time, as well as how often they had difficultly falling or staying asleep, waking up early or experiencing tiredness.

It identified those who said they experienced such issues at least three nights or days a week, for at least three months as experiencing insomnia.

While the study found a link between bedtime screen use and people reporting sleep disruption or insomnia, researchers say it does not mean it is a cause.

“This study cannot determine causality — for example, whether screen use causes insomnia or if students with insomnia use screens more,” said Dr Hjetland.

They also note that the study’s reliance on survey data of self-reported experiences may mean it contains biases, and its findings should not be considered globally representative.

Joshua Piper, a sleep clinician at ResMed UK, said the study provided “valuable, mounting evidence” of electronic device use negatively impacting sleep.

“It steals both opportunity and the quality of your sleep, which is why some may struggle for onset, others struggle to stay asleep,” he told the BBC.

While people may try to mitigate the impact by adjusting screen brightness or using night mode, Mr Piper said previous studies suggested it was scrolling and engaging with a device that was likely to cause sleep disruptions.

Tips for better sleep

Insomnia is believed to affect as many as one in three people in the UK.

The sleep disorder is among a whole host of problems people have reported experiencing with sleep – with late night phone use and doomscrolling often blamed.

While common practice, the actual impact of using social media or scrolling through online content in bed on physical and mental health remains contested.

Still, experts recommend that people stop using digital devices shortly before trying to go to sleep.

They also say establishing a routine by going to bed and getting up at the same time every day may help improve sleep.

Mental health charities Mind and Rethink recommend trying to do something relaxing before going to sleep such as breathing exercises, reading a book or having a bath, rather than trying to force yourself to sleep.

They also suggest avoiding caffeine, alcohol or large meals before bed, doing gentle exercise and trying to make your bedroom more comfortable, where possible.

Sleep therapist Dr Kat Lederle told the BBC that getting exposure to natural daylight, particularly in the morning, was vital to help regulate our internal body clock.

She said finding ways to “let go of the busy, thinking day”, such as by doing an enjoyable activity that is not too stimulating, can also be key to better sleep.

The authors of this study echo the need for further research into the subject, including longer-term monitoring of sleep patterns as well as investigations into areas such as the disruption caused overnight by device notifications.

“Together, such efforts could clarify the impact of bedtime screen use on sleep and inform targeted recommendations for students and other populations,” they conclude.

Breakthrough: New blood test can diagnose and track the progression of Alzheimer’s

A new blood test could revolutionize the diagnosis and treatment of Alzheimer’s. Beyond confirming the presence of the disease, the test also helps determine the stage of its progression. This may fundamentally change how physicians manage Alzheimer’s care.

The test was developed by experts at Washington University School of Medicine in St. Louis and Lund University in Sweden. Their studies indicate that a particular blood protein, MTBR-tau243, can be used to monitor the extent of dangerous tau accumulation in the brain.

The tangles of tau protein are some of the hallmark characteristics of Alzheimer’s and are directly proportional to the intensity of the symptoms.

This new technique is considerably more convenient than brain scans since it is non-invasive, and does not require expensive procedures that are difficult to access.

Tracking Alzheimer’s with a blood test

Right now, doctors can use several blood tests to help detect Alzheimer’s. Some of the tests that are already in use are based on earlier discoveries at Washington University.

These tests look for early warning signs but don’t reveal how much the disease has progressed. That’s a crucial gap. Alzheimer’s treatments are most helpful in the early stages, before too much damage has been done.

Having a way to tell whether someone is in an early or late phase of the disease would help doctors decide which treatment would work best. It could also clarify whether a person’s memory or thinking issues are actually caused by Alzheimer’s or something else.

“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” said co-senior author Dr. Randall J. Bateman.

“In clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients.”

A reliable way to monitor the disease

Alzheimer’s typically starts with a buildup of amyloid protein in the brain. Tau tangles develop later and mark the point when symptoms begin to show.

The best way to see these changes has been through PET scans, which can track amyloid and tau deposits. But these scans are expensive, time-consuming, and often only available in large hospitals or research centers. That’s why scientists have been working on blood-based alternatives.

The team had already developed blood tests that measure amyloid plaque buildup. Earlier research showed that levels of MTBR-tau243 in spinal fluid could match up with brain tau levels.

In this new study, the researchers demonstrated that they could get the same results using blood samples. A blood draw is much easier and more accessible than a spinal tap.

Testing the new approach

To validate the test, the researchers used data from two groups of people. One group came from a research center at Washington University and included 108 volunteers. The other group included 55 people from a Swedish study known as BioFINDER-2.

Next, the experts checked their findings with data from 739 additional people in the BioFINDER-2 group.

These participants represented a range of Alzheimer’s stages – from people who had no symptoms but had amyloid in their brains, to those with mild cognitive issues, to people with full dementia.

The study also included individuals with memory or thinking problems due to other conditions, and some who were cognitively healthy.

Alzheimer’s progression revealed in blood

The results were promising. MTBR-tau243 levels in the blood matched the amount of tau tangles in the brain with 92% accuracy.

In healthy people and those in the earliest stage of the disease, the levels were normal. But in people showing symptoms, the protein levels were clearly elevated – and much higher in those with advanced disease.

This difference made it easy to tell who was in an early or late stage of Alzheimer’s. It also helped distinguish Alzheimer’s dementia from other kinds of cognitive problems.

That kind of clarity could make a huge difference in choosing the right treatment path.

A tool for personalized Alzheimer’s care

The new test uses technology licensed by Washington University to C2N Diagnostics, which previously developed similar blood tests for amyloid plaques. The earlier tests were designed to detect another tau protein called p-tau217.

“I believe we will use blood-based p-tau217 to determine whether an individual has Alzheimer’s disease, but MTBR-tau243 will be a highly valuable complement in both clinical settings and research trials,” said Oskar Hansson, a professor of neurology at Lund University.

“When both of these biomarkers are positive, the likelihood that Alzheimer’s is the underlying cause of a person’s cognitive symptoms increases significantly, compared to when only p-tau217 is abnormal. This distinction is crucial for selecting the most appropriate treatment for each patient.”

Looking ahead to better treatments

Currently, there are two FDA-approved drugs that target amyloid in the brain to slow Alzheimer’s. But more treatments are being tested – including ones that aim at tau protein and other disease mechanisms.

As these therapies become available, doctors will need reliable ways to match the right treatment to each stage of the disease. Blood tests could be the key to this shift toward personalized Alzheimer’s care.

“We’re about to enter the era of personalized medicine for Alzheimer’s disease,” said Kanta Horie, a research associate professor of neurology at WashU Medicine.

“For early stages with low tau tangles, anti-amyloid therapies could be more efficacious than in late stages. But after the onset of dementia with high tau tangles, anti-tau therapy or one of the many other experimental approaches may be more effective.”

“Once we have a clinically available blood test for staging, plus treatments that work at different stages of the disease, doctors will be able to optimize their treatment plans for the specific needs of each patient.”

The full study was published in the journal Nature Medicine.

Food and fuel that farms itself: Genome sequences of five duckweed species reveal basis for unique plant traits

Under the right conditions, duckweed essentially farms itself. Wastewater, ponds, puddles, swamps—you name it. If there’s enough sunlight and carbon dioxide, the aquatic plant can grow freely. But that’s not all that makes it intriguing. Packed inside duckweed’s tiny fronds is enormous potential as a soil enricher, a fuel source, protein-rich foods, and more. New findings at Cold Spring Harbor Laboratory (CSHL) could help bring all that potential to life. The research is published in the journal Current Biology.

CSHL Professor and HHMI Investigator Rob Martienssen and Computational Analyst Evan Ernst started working with duckweed over 15 years ago. They see their latest research as one of the most important and eye-opening studies on the plant to date. The team has developed new genome sequences for five duckweed species. The sequences reveal several genes that—when present or absent—may be behind the plant’s unique traits and versatility.

Martienssen explains, “The use of cutting-edge technology allowed us to make a catalog of genes that was extremely accurate. We could tell exactly which genes were there and which were not. A lot of genes that are missing are responsible for features of the plant—open stomata or the lack of roots. We could identify genes that were responsible for each trait.”

Stomata are pores on the surface of plants. They’re crucial for taking in carbon dioxide and releasing oxygen. Open stomata allow for greater intake, making them valuable for carbon capture technology. A lack of roots in some species further increases duckweed’s potential, making it easier for the plant to thrive in any watery environment.

Other species possess traits that showcase duckweed’s potential as a food and fuel source. Some traits promote high protein production, allowing for use as animal feed. Others promote starch accumulation, making the plant ripe for biofuel production. Several industries have taken notice. For now, they’re mostly concerned with the duckweed growing in their backyards.

Ernst explains, “Duckweed agriculture is in a nascent stage. Commercial growers are working with different species in the field, evaluating them in their own local situation. There’s so much variation within one species of duckweed—as much as you can find across all the species. So, having multiple genomes for multiple species is critical.”

Martienssen and Ernst hope their genomes will open the door to a new world of commercial applications. That said, their research may tell us as much about the plant’s past. Their study hints at how duckweed split off into different species 59 million years ago. Earth’s climate was quite extreme back then, so duckweed’s genes just might say something about the planet’s future, too.

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