Publisher Health

Texas A&M AgriLife Research study may lead to novel obesity treatment New study provides insights on role of ‘hunger hormone’ receptor in obesity-realted chronic inflammation
A team comprised primarily of Texas A&M AgriLife Research scientists has made an important discovery that could lead to a novel treatment for obesity and obesity-associated diseases or conditions.
Details of the discovery can be found in the study “Nutrient-sensing growth hormone secretagogue receptor in macrophage programming and meta-inflammation,” published in the January issue of Molecular Metabolism.
Yuxiang Sun, Ph.D., is the lead investigator on a study that could lead to a novel treatment for obesity and obesity-associated diseases or conditions. (Texas A&M AgriLife photo by Michael Miller)
“Chronic inflammation commonly associated with obesity is a key reason obese individuals often have many other chronic diseases,” said Yuxiang Sun, Ph.D., professor and AgriLife Research Faculty Fellow in the Texas A&M College of Agriculture and Life Sciences Department of Nutrition and associate member of the Texas A&M Institute for Advancing Health Through Agriculture, IHA.
Sun, who served as lead investigator for the study, was among several investigators from the Department of Nutrition. Study contributions were also made by other entities in The Texas A&M University System.
Competitive funding for the study came from the National Institutes of Health. It was also supported by the IHA — the world’s first research institute to bring together precision nutrition, responsive agriculture and behavioral research to reduce diet-related chronic diseases.

About the study
The study focused on the role of one molecule involved in how our bodies deal with hunger: the growth hormone secretagogue receptor, GHSR, which mediates the effect of ghrelin, known as the “hunger hormone.” Studies have shown that ghrelin promotes eating and increases fat. Ghrelin activates GHSR to increase appetite, fat accumulation and insulin resistance.
Research has shown that under normal conditions, GHSR is highly active in the brain but much less active in other tissues such as liver and fat, also referred to as adipose tissue. For this reason, most ghrelin research has focused on the brain.
“Intriguingly, in previous research, we found the complete removal of GHSR protects against diet-induced inflammation and insulin resistance in adipose tissue and the liver without affecting food intake,” Sun said. “This was very puzzling because that GHSR has very low expression in fat and liver cells.”
A link between obesity and the immune system
Sun and her team has made the novel observation that GHSR activity in macrophages — a major immune cell type in tissues — increases dramatically under the condition of obesity. In this study, Sun’s team investigated whether ghrelin’s effect in adipose tissues and the liver was due to the infiltration of GHSR-expressing macrophages into these tissues under the condition of obesity.

“If that was the case, this infiltration by those particular GHSR-expressing macrophages would trigger chronic inflammation and insulin resistance,” Sun said.
Study results and implications
To understand the role of GHSR in macrophages, the team developed a unique animal model to selectively shut down GHSR activity in macrophages.
“Indeed, our study results showed that macrophage-specific GHSR deficiency reduces diet-induced systemic inflammation and insulin resistance,” Sun said. “Remarkably, GHSR deficiency in macrophages reduced diet-induced macrophage infiltration, macrophage activation and fat deposition in adipose tissue and the liver.”
In addition to their effect on diet-induced chronic inflammation, the study also demonstrated that GHSR-deficient macrophages protect against acute inflammation induced by bacterial toxins.
At a molecular level, they found GHSR programs macrophages through an insulin signaling pathway, Sun said. Basically, this study showed that macrophage GHSR controls chronic inflammation in obesity by regulating macrophage programming.
She said the study’s novel results demonstrate that macrophage GHSR plays a key role in meta-inflammation by promoting macrophage infiltration and inflammatory activation.
“These exciting new findings helped to resolve a long-time mystery of GHSR in adipose tissue and the liver in obesity, by uncovering the novel immunoregulatory role of GHSR and revealing that GHSR signaling is a critical link between metabolism and immunity,” Sun said.
She said the study adds a new dimension to the biology of ghrelin, and underscores that ghrelin is not only a hunger hormone, but also an important nutrient-sensor and immune regulator.
“This has profound implications for health and disease, as blocking GHSR in macrophages may serve as a promising immune therapy to prevent or treat obesity, diabetes and inflammation,” Sun said.

You may have heard about the gut microbiome and its influence on a person’s overall health and well-being. It turns out that the same may hold true for the semen microbiome.
According to researchers from the Department of Urology at UCLA, the semen microbiota might play a crucial role in influencing sperm parameters and enhancing male fertility. Considering recent studies highlighting the microbiome’s significance in overall human health, researchers investigated the semen microbiome to understand its potential impact on male infertility. Exploring the functions of these microorganisms in semen could potentially pave the way for developing treatments targeted at rectifying any issues with sperm parameters.
The study found that one microbe in particular, Lactobacillus iners, may have a direct negative impact on male fertility. Researchers found that men with more of this microbe were more likely to have issues with sperm motility. Previous research revealed that Lactobacillus iners can preferentially produce L-lactic acid, potentially leading to a pro-inflammatory environment locally, which could adversely affect sperm motility. The study authors point out that existing research has hinted at the link between this microbe and fertility, but most of the literature pertains to the vaginal microbiome and female factors. This is the first study to report a negative association between the microbe and male-factor fertility.
Researchers also discovered that three types of bacteria in the Pseudomonas group were present in patients with both normal and abnormal sperm concentrations. Microbes called Pseudomonas fluorescens and Pseudomonas stutzeri were more common in patients with abnormal sperm concentrations, while Pseudomonas putida was less common in samples with abnormal sperm concentrations. However, the findings indicate that not every member of the same closely related group may affect fertility in the same way, whether positively or negatively. In other words, even closely related microbes may not always have the same direct correlation to fertility.
“There is much more to explore regarding the microbiome and its connection to male infertility,” said Vadim Osadchiy, a resident in the Department of Urology at UCLA and the lead author of the study. “However, these findings provide valuable insights that can lead us in the right direction for a deeper understanding of this correlation. Our research aligns with evidence from smaller studies and will pave the way for future, more comprehensive investigations to unravel the complex relationship between the semen microbiome and fertility.”

Newly released documents indicate that a U.S. genetic database had received the sequence of the coronavirus two weeks before it was made public by others.In late December 2019, eight pages of genetic code were sent to computers at the National Institutes of Health in Bethesda, Md.Unbeknown to American officials at the time, the genetic map that had landed on their doorstep contained critical clues about the virus that would soon touch off a pandemic.The genetic code, submitted by Chinese scientists to a vast public repository of sequencing data run by the U.S. government, described a mysterious new virus that had infected a 65-year-old man weeks earlier in Wuhan. At the time the code was sent, Chinese officials had not yet warned of the unexplained pneumonia sickening patients in the central city of Wuhan.But the U.S. repository, which was designed to help scientists share run-of-the-mill research data, never added the submission it received on Dec. 28, 2019, to its database. Instead, it asked the Chinese scientists three days later to resubmit the code with certain additional technical details. That request went unanswered.It took almost another two weeks for a separate pair of virologists, one Australian and the other Chinese, to work together to post the genetic code of the new coronavirus online, setting off a frantic global effort to save lives by building tests and vaccines.The initial attempt by Chinese scientists to publicize the crucial code was revealed for the first time in documents released on Wednesday by House Republicans investigating Covid’s origins. The documents reinforced questions circulating since early 2020 about when China learned of the virus that was causing its unexplained outbreak — and also drew attention to gaps in the American system of monitoring for dangerous new pathogens.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

Most people infected with the SARS-CoV-2 virus recover after the acute illness. However, a significant proportion of infected individuals develop long-lasting symptoms with a wide range of manifestations. The causes and disease mechanisms of Long Covid are still unknown, and there are no diagnostic tests or targeted treatments.
Part of the immune system active for too long
A team of researchers led by Onur Boyman, professor of immunology at the University of Zurich (UZH) and Director of the Department of Immunology at the University Hospital Zurich (USZ), has shown in a study that the complement system plays an important role in Long Covid. It is part of the innate immune system and normally helps to fight infections and eliminate damaged and infected body cells. “In patients with Long Covid, the complement system no longer returns to its basal state, but remains activated and, thus, also damages healthy body cells,” says Boyman.
Continued activation of complement system damages tissue and blood cells
The researchers followed 113 COVID-19 patients for up to one year after their acute SARS-CoV-2 infection and compared them with 39 healthy controls. After six months, 40 patients had active Long Covid disease. More than 6,500 proteins in the blood of the study participants were analyzed both during the acute infection and six months later. “The analyses of which proteins were altered in Long Covid confirmed the excessive activity of the complement system. Patients with active Long Covid disease also had elevated blood levels indicating damage to various body cells, including red blood cells, platelets and blood vessels,” explains Carlo Cervia-Hasler, a postdoctoral researcher in Boyman’s team and first author of the study.
Bioinformatics recognizes protein patterns
The measurable changes in blood proteins in active Long Covid indicate an interaction between proteins of the complement system, which are involved in blood clotting and the repair of tissue damage and inflammation. In contrast, the blood levels of Long Covid patients who recovered from the disease returned to normal within six months. Active Long Covid is therefore characterized by the protein pattern in the blood. The blood markers were discovered using bioinformatics methods in collaboration with Karsten Borgwardt during his time as a professor at ETH Zurich.
Improved diagnostics and new therapeutic approaches
“Our work not only lays the foundation for better diagnosis, but also supports clinical research into substances that could be used to regulate the complement system. This opens up new avenues for the development of more targeted therapies for patients with Long Covid,” summarizes Onur Boyman.

University of North Carolina at Chapel Hill scientists created a new drug delivery system, called the Spatiotemporal On-Demand Patch (SOP), which can receive commands wirelessly from a smartphone or computer to schedule and trigger the release of drugs from individual microneedles. The patch’s thin, soft platform resembles a Band-Aid and was designed to enhance user comfort and convenience, since wearability is a crucial factor for chronically ill patients.
The research team, led by Juan Song, PhD, professor of pharmacology at the UNC School of Medicine, and Wubin Bai, PhD, assistant professor of applied physical sciences at the UNC College of Arts and Sciences, tested the SOP in a mouse model, using melatonin in the microneedles to improve sleep.
This research, published in the journal Nature Communications, opens the door to researching this wirelessly controlled patch to deliver on-demand treatments for neurodegenerative disorders, including Alzheimer’s disease. To that end, the UNC School of Medicine and UNC Health funded a $25,000 pilot project to test the SOP in a mouse model of Alzheimer’s disease.
“SOP’s ability to enable joint delivery of multiple drugs could address various aspects of Alzheimer’s Disease, such as reducing beta-amyloid plaques, mitigating neuroinflammation and enhancing cognitive function,” said Bai, a co-senior author.
The open access paper titled, “Digital Automation of Transdermal Drug Delivery with High Spatiotemporal Resolution,” was co-authored by Yihang Wang of the Department of Applied Physical Sciences and Zeka Chen of the Department of Pharmacology. Bai said the research highlights not only a multidisciplinary collaboration but also a “passionate involvement of Carolina undergraduate students,” including Priyash Hafiz of the Department of Applied Physical Sciences, and Brayden Davis, Will Lipman, Tian Wang and Sicheng Xing of the UNC/NCSU Joint Department of Biomedical Engineering.
The patch, which has received a provisional patent, enables highly localized treatment — less than 1 square millimeter — of specific tissues, organs or regions within the body, and drug release can be triggered within 30 seconds in response to an electrical signal. Patients could wear more than one patch at a time which would reduce the need for doctors’ visits, or even trips to the hospital, for medical attention.
“The beauty of this device is that it can house dozens, if not hundreds, of concentrated drugs and can program their sequential release automatically,” said Song, who is a member of the UNC Neuroscience Center. “Rapid drug release can be crucial in emergency situations or when immediate therapeutic action is required.”
The microneedles are coated with gold, which protects the drugs and surrounding tissues. When a low-voltage electrical stimulus is applied through the patch, the gold coating disintegrates, exposing the drug-loaded microneedles to the skin and initiating the controlled release of the drugs.

“This level of specificity ensures precise and customized drug delivery, catering to the needs of different conditions or specific regions of the body,” said Wang. “This offers a novel approach to achieving controlled drug release through a combination of materials science and electrical engineering.”
The National Science Foundation and the National Institutes of Health funded this research.
David DeFusco, communications specialist at the UNC Department of Applied Physical Sciences, wrote the original news announcement. The UNC School of Medicine contact is Mark Derewicz, director of research and national news for UNC Health.

Electrical deep brain stimulation (DBS) is a well-established method for treating disordered movement in Parkinson’s disease. However, implanting electrodes in a person’s brain is an invasive and imprecise way to stimulate nerve cells. Researchers report in ACS’ Nano Letters a new application for the technique, called magnetogenetics, that uses very small magnets to wirelessly trigger specific, gene-edited nerve cells in the brain. The treatment effectively relieved motor symptoms in mice without damaging surrounding brain tissue.
In traditional DBS, a battery pack externally sends electrical signals through wires, activating nerve cells in a region of the brain called the subthalamic nucleus (STN). STN activation can relieve motor symptoms of Parkinson’s disease, including tremors, slowness, rigidity and involuntary movements. However, because the potential side effects, including brain hemorrhage and tissue damage, can be severe, DBS is usually reserved for people who have late-stage Parkinson’s disease or when symptoms are no longer manageable with medication. In a step toward a less invasive treatment, Minsuk Kwak and Jinwoo Cheon worked with their colleagues to develop a wireless method to effectively reduce motor dysfunction in people with Parkinson’s disease.
For their wireless technique, the researchers tagged nanoscale magnets with antibodies to help the molecules “stick” to the surface of STN nerve cells. Then they injected the sticky magnets into the brains of mice with early- and late-stage Parkinson’s disease. Prior to the injection in the STN, those same nerve cells had been modified with a gene that caused them to activate when the modified magnets on the cell’s surface twisted in reaction to an externally applied magnetic field of about 25 milliteslas, which is about one- thousandth the strength of an MRI.
In demonstrations of the magnetized and modified neurons in mice with Parkinson’s disease, the mice exposed to a magnetic field showed improved motor function to levels comparable to those of healthy mice. The team observed that mice that received multiple exposures to the magnetic field retained more than one-third of their motor improvements while mice that received one exposure retained almost no improvements. Additionally, the nerve cells of treated mice showed no significant damage in and around the STN, which suggests this could be a safer alternative to traditional implanted DBS systems, the researchers say. The team believes its wireless magnetogenetic approach has therapeutic potential and could be used to treat motor dysfunction in people with early- or late-stage Parkinson’s disease as well as other neurological disorders, such as epilepsy and Alzheimer’s disease.
The authors acknowledge funding from the Institute for Basic Science.

Viral respiratory infections are a significant public health concern. A study publishing January 18 in the open access journal PLOS Biology by Marta Galanti at Columbia University, New York, United States and colleagues used longitudinal cohort data to create an interactive, publicly-available website, The Virome of Manhattan Project: Virome Data Explorer to visualize cohort characteristics, infection events, and illness severity factors.
Viral respiratory infections may lead to severe outcomes. However, better understanding of host response, host genetic makeup, and bacterial coinfections is required to develop effective therapeutics. In order to contribute to epidemiological research on factors contributing to disease severity, the researchers conducted a longitudinal cohort study, surveilling respiratory viruses for 19 months between 2016-2018 in New York City. They analyzed over 800 nasopharyngeal samples with clinical data, including self-reported symptoms from 214 participants. From these data, researchers created the Virome Data Explorer, a publicly-available database. Users can access cohort data to visualize and analyze changes and patterns in infections, symptoms, and illness outcomes.
While the database shares important cohort data related to infections, symptoms, and gene activity, the project has several limitations. Adults over the age of 65 were excluded from the cohort, even though according to the authors, respiratory viruses may lead to “extremely serious complications, particularly in infants, elders, and immunocompromised hosts.” Ages of children under 10 were not stratified, obscuring symptom and illness information specific to infants, another high-risk demographic. Vaccination status, immunocompromised conditions, and medicine uptake during infection course were also not among the data collected from study participants, which may limit the applications of the Virome Data Explorer.
According to the authors, “We present a cohort study, consisting of hundreds of samples, that depicts the transcriptional changes driven by respiratory viral infection. We have compiled these data to build a publicly-available, user-friendly web-based resource where any user can compare, longitudinally over the course of 19 months, patterns of viral positivity, symptomatology and transcriptomic changes for the individuals enrolled.”
The authors add, “This is a resource paper aiming at characterizing the host response to common and often asymptomatic viral respiratory infections. We collected and made available a 2-year longitudinal dataset including molecular data and symptoms records for over 100 participants from different age groups in NYC.”

Across 21 licensed premises in England, removing the largest individual serving size of wine from the menu reduced the volume of wine sold, according to a new study publishing January 18 in the open access journal PLOS Medicine by Theresa Marteau of the University of Cambridge, UK, and colleagues.
Alcohol consumption is the fifth largest contributor to premature death and disease globally. Many cues in physical and economic environments influence alcohol consumption across populations. One proposed intervention to excessive alcohol consumption is reducing the size of servings of alcoholic drinks sold by the glass, but there has been no real-world evidence for the effectiveness of this.
In the new study, researchers asked 21 licensed premises in England to remove from their menus their largest serving of wine by the glass — usually 250 mL — for four weeks. The researchers then tracked the total volume of wine, beer and cider sold by each establishment.
Over the course of the four weeks, the total volume of wine sold by the licensed premises decreased by 7.6%, and there was no overall increase in beer and cider sales. There was an increase in the sales of smaller servings of wine by the glass — generally 125 mL and 175 mL — but no impact on sales of wine by the bottle or beer or cider sales. Despite the decreased volume of wine sold, there was no change in daily revenue, likely reflecting an increased profit margin for smaller glasses of wine. Overall, the study suggests that when the largest serving of wine is not available, people shifted toward the smaller options and ultimately drank less alcohol.
“This suggests that this is a promising intervention for decreasing alcohol consumption across populations, which merits consideration as part of alcohol licensing regulations,” the authors say.
Marteau adds, “Removing the largest serving size of wine by the glass in 21 licensed premises reduced the volume of wine sold, in keeping with the wealth of research showing smaller serving sizes reduce how much we eat. This could become a novel intervention to improve population health by reducing how much we drink.”

Temperature, day length and humidity have been found to be linked to the increased spread of a diarrheal illness a new study from the University of Surrey reveals. The findings could help predict further outbreaks of the illness, potentially leading to better preparedness within health services.
During this unique study, researchers led by Dr Giovanni Lo Iacono, investigated the impact of weather on the transmission of campylobacteriosis, a bacterial infection which can cause diarrhea and stomach pains. According to the World Health Organisation, Campylobacter infections are the most common causes of human bacterial gastroenteritis in the world. Infections are generally mild, but can be fatal among very young children, elderly, and immunosuppressed individuals.
Dr Giovanni Lo Iacono, Senior Lecturer in Biostatistics and Epidemiology, in the School of Veterinary Medicine at the University of Surrey and who contributed to the recent UKSHA Health Effects of Climate Change, said:
“Since Hippocrates, there has been a large consensus that weather and climate influence the spread of diseases. Getting to the bottom of why this is and what specific environmental factors drive the spread of disease is a complicated matter and not fully understood. We now have a detailed description of how the weather affects the disease, and the next step is to understand the why. Importantly, through our transparent and conceptually simple approach, we can now tell the risk of getting the disease when we know the recent local weather.
“This information is invaluable, as illnesses such as campylobacteriosis not only cause discomfort to individuals, but have enormous societal impacts, with people having to call in sick to work and puts extra pressure on health services across the world.”
To determine if weather impacts incidence of campylobacteriosis, researchers analysed data from approximately one million cases of campylobacteriosis in England and Wales over a 20-year period from UKHSA. An innovative mathematical model was developed by the team enabling them to compare this data provided by the Met Office with weather parameters at the time.
Analysis of this data showed incidents of campylobacteriosis were consistent below temperatures of eight degrees Celsius. However, a sharp increase in infection (approximately one case per million) were observed for every five degree rise in temperature, where temperatures were between eight to 15 degrees Celsius. A link to humidity was identified by the team who also observed high incidents of infection when levels of water vapour in the air were between 75- 80 percent.

Interestingly, researchers observed strong associations between day length (longer than 10 hours) and increased cases of the illness. This association was further strengthened when humidity was also high. Rainfall and wind- speed were not strongly linked to the spread of campylobacteriosis.
Dr Lo Iacono, added:
“What we have found is that rising temperatures, humidity and increased day length are associated with the spread of campylobacteriosis. We do not fully understand why this may be. It could be that warm weather increases the survival and spread of pathogenic bacteria (so the weather causes the disease) or alternatively it could be people’s behaviour and how they socialise during such periods.
“However, what we do know is climate change not only has an environmental impact but has the potential to negatively affect our health by aiding the spread of infectious diseases.”
Gordon Nichols, a visiting Professor at the University of Surrey, said:
“Environmental data can help us understand complex patterns in the spreads of diseases. Having this knowledge is invaluable as it can help us identify areas vulnerable to potential outbreaks and ensure they have the resources available to treat people affected and to curb the spread of disease into other areas.”

Tumors constantly shed DNA from dying cells, which briefly circulates in the patient’s bloodstream before it is quickly broken down. Many companies have created blood tests that can pick out this tumor DNA, potentially helping doctors diagnose or monitor cancer or choose a treatment.
The amount of tumor DNA circulating at any given time, however, is extremely small, so it has been challenging to develop tests sensitive enough to pick up that tiny signal. A team of researchers from MIT and the Broad Institute of MIT and Harvard has now come up with a way to significantly boost that signal, by temporarily slowing the clearance of tumor DNA circulating in the bloodstream.
The researchers developed two different types of injectable molecules that they call “priming agents,” which can transiently interfere with the body’s ability to remove circulating tumor DNA from the bloodstream. In a study of mice, they showed that these agents could boost DNA levels enough that the percentage of detectable early-stage lung metastases leapt from less than 10 percent to above 75 percent.
This approach could enable not only earlier diagnosis of cancer, but also more sensitive detection of tumor mutations that could be used to guide treatment. It could also help improve detection of cancer recurrence.
“You can give one of these agents an hour before the blood draw, and it makes things visible that previously wouldn’t have been. The implication is that we should be able to give everybody who’s doing liquid biopsies, for any purpose, more molecules to work with,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.
Bhatia is one of the senior authors of the new study, along with J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering at MIT and a member of the Koch Institute and the Ragon Institute of MGH, MIT, and Harvard and Viktor Adalsteinsson, director of the Gerstner Center for Cancer Diagnostics at the Broad Institute.
Carmen Martin-Alonso PhD ’23, MIT and Broad Institute postdoc Shervin Tabrizi, and Broad Institute scientist Kan Xiong are the lead authors of the paper, which appears today in Science.

Better biopsies
Liquid biopsies, which enable detection of small quantities of DNA in blood samples, are now used in many cancer patients to identify mutations that could help guide treatment. With greater sensitivity, however, these tests could become useful for far more patients. Most efforts to improve the sensitivity of liquid biopsies have focused on developing new sequencing technologies to use after the blood is drawn.
While brainstorming ways to make liquid biopsies more informative, Bhatia, Love, Adalsteinsson, and their trainees came up with the idea of trying to increase the amount of DNA in a patient’s bloodstream before the sample is taken.
“A tumor is always creating new cell-free DNA, and that’s the signal that we’re attempting to detect in the blood draw. Existing liquid biopsy technologies, however, are limited by the amount of material you collect in the tube of blood,” Love says. “Where this work intercedes is thinking about how to inject something beforehand that would help boost or enhance the amount of signal that is available to collect in the same small sample.”
The body uses two primary strategies to remove circulating DNA from the bloodstream. Enzymes called DNases circulate in the blood and break down DNA that they encounter, while immune cells known as macrophages take up cell-free DNA as blood is filtered through the liver.
The researchers decided to target each of these processes separately. To prevent DNases from breaking down DNA, they designed a monoclonal antibody that binds to circulating DNA and protects it from the enzymes.

“Antibodies are well-established biopharmaceutical modalities, and they’re safe in a number of different disease contexts, including cancer and autoimmune treatments,” Love says. “The idea was, could we use this kind of antibody to help shield the DNA temporarily from degradation by the nucleases that are in circulation? And by doing so, we shift the balance to where the tumor is generating DNA slightly faster than is being degraded, increasing the concentration in a blood draw.”
The other priming agent they developed is a nanoparticle designed to block macrophages from taking up cell-free DNA. These cells have a well-known tendency to eat up synthetic nanoparticles.
“DNA is a biological nanoparticle, and it made sense that immune cells in the liver were probably taking this up just like they do synthetic nanoparticles. And if that were the case, which it turned out to be, then we could use a safe dummy nanoparticle to distract those immune cells and leave the circulating DNA alone so that it could be at a higher concentration,” Bhatia says.
Earlier tumor detection
The researchers tested their priming agents in mice that received transplants of cancer cells that tend to form tumors in the lungs. Two weeks after the cells were transplanted, the researchers showed that these priming agents could boost the amount of circulating tumor DNA recovered in a blood sample by up to 60-fold.
Once the blood sample is taken, it can be run through the same kinds of sequencing tests now used on liquid biopsy samples. These tests can pick out tumor DNA, including specific sequences used to determine the type of tumor and potentially what kinds of treatments would work best.
Early detection of cancer is another promising application for these priming agents. The researchers found that when mice were given the nanoparticle priming agent before blood was drawn, it allowed them to detect circulating tumor DNA in blood of 75 percent of the mice with low cancer burden, while none were detectable without this boost.
“One of the greatest hurdles for cancer liquid biopsy testing has been the scarcity of circulating tumor DNA in a blood sample,” Adalsteinsson says. “It’s thus been encouraging to see the magnitude of the effect we’ve been able to achieve so far and to envision what impact this could have for patients.”
After either of the priming agents are injected, it takes an hour or two for the DNA levels to increase in the bloodstream, and then they return to normal within about 24 hours.
“The ability to get peak activity of these agents within a couple of hours, followed by their rapid clearance, means that someone could go into a doctor’s office, receive an agent like this, and then give their blood for the test itself, all within one visit,” Love says. “This feature bodes well for the potential to translate this concept into clinical use.”
The researchers have launched a company called Amplifyer Bio that plans to further develop the technology, in hopes of advancing to clinical trials.
“A tube of blood is a much more accessible diagnostic than colonoscopy screening or even mammography,” Bhatia says. “Ultimately, if these tools really are predictive, then we should be able to get many more patients into the system who could benefit from cancer interception or better therapy.”
The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, the Marble Center for Cancer Nanomedicine, the Gerstner Family Foundation, the Ludwig Center at MIT, the Koch Institute Frontier Research Program via the Casey and Family Foundation, and the Bridge Project, a partnership between the Koch Institute and the Dana-Farber/Harvard Cancer Center.