Researchers engineer in vivo delivery system for prime editing, partially restoring vision in mice

By adapting virus-like particles to carry the machinery for a type of gene editing called prime editing, scientists have corrected disease-causing mutations in animals and increased editing efficiency.

Peer-Reviewed Publication

BROAD INSTITUTE OF MIT AND HARVARD

Prime editing, a versatile form of gene editing that can correct most known disease-causing genetic mutations, now has a new vehicle to deliver its machinery into cells in living animals.

A team of researchers at the Broad Institute of MIT and Harvard has engineered virus-like particles to deliver prime editors to cells in mice at a high enough efficiency to rescue a genetic disorder. In the new work published today in Nature Biotechnology, the team adapted engineered virus-like particles (eVLPs) that they had previously designed to carry base editors — another type of precision gene editor that makes single-letter changes in DNA. 

Now the researchers describe how they re-engineered both eVLPs and parts of the prime editing protein and RNA machinery to boost editing efficiency up to 170 times in human cells compared to the previous eVLPs that deliver base editors. The team used their new system to correct disease-causing mutations in the eyes of two mouse models of genetic blindness, partially restoring their vision. They also delivered prime editors to the mouse brain, and did not detect any off-target editing.

“This study represents the first time to our knowledge that delivery of protein-RNA complexes has been used to achieve therapeutic prime editing in an animal,” said David Liu, senior author of the study and Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad. Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.

Delivery dilemma

Gene editing approaches promise to treat a range of diseases by precisely correcting genetic mutations that cause disease. Prime editing, described in 2019 by Liu’s group, can make longer and more diverse types of DNA changes than other types of editing. However, delivering the complex gene editing machinery to cells in living animals has been challenging.

The prime editing system has three components: a Cas9 protein that can nick DNA; an engineered prime editing guide RNA (pegRNA) that specifies the location of the edit and also contains the new edited sequence to install at that location; and a reverse transcriptase that uses the pegRNA as a template to make specific changes to the DNA.

Researchers have used a variety of methods to deliver these molecular machines to cells, including lipid nanoparticles and viruses. Virus-like particles (VLPs), composed of a shell of viral proteins that carry cargo but lack any viral genetic material, have also been of particular interest. But VLPs have traditionally yielded modest delivery outcomes in animals, and have to be specifically engineered for each different type of cargo to efficiently deliver to cells.

“We initially hoped that we could just take the eVLPs that we had painstakingly developed and optimized for base editing and apply them to prime editors,” said Meirui An, a graduate student in the Liu lab and first author of the new paper. “But when we tried that, we observed almost no prime editing at all.”

Bottleneck breakthroughs

In the new work, the researchers extensively re-engineered both the eVLP proteins and the prime editing machinery itself so that both the delivery and editing systems worked more efficiently. For instance, they improved how the prime editing cargo was packaged in the eVLPs, how it was separated from the delivery vehicle, and how it was delivered into the target cells’ nuclei.

“The prime editor cargo must be efficiently packaged into eVLPs when the particles form but must also be efficiently released from the particles after target cell entry,” said Aditya Raguram, a former Liu lab graduate student and co-author of the study. “All of these steps have to be carefully orchestrated in order to achieve efficient eVLP-mediated prime editing.”

While each individual improvement led to small jumps in the efficiency of the prime editors, the changes together had a much larger impact.

“When we combined everything together, we saw improvements of roughly 100-fold compared to the eVLPs that we started with,” said Liu. “That kind of improvement in efficiency should be enough to give us therapeutically relevant levels of prime editing, but we didn’t know for sure until we tested it in animals.”

In vivo tests

Liu and his colleagues, in collaboration with Krzysztof Palczewski of the University of California, Irvine, first tested the system in mice to correct two different genetic mutations in the eyes. One mutation, in the gene Mfrp, causes a disease called retinitis pigmentosa that leads to progressive retinal degeneration. The other, in the gene Rpe65, is associated with blindness seen in the condition known as Leber congenital amaurosis (LCA) in humans.

In both instances, the eVLPs corrected the mutation in up to 20 percent of the animals’ retina cells, partially restoring their vision.

The research group also showed that the eVLPs loaded with prime editing machinery could effectively edit genes in the brains of living mice. Nearly half of all cells in the cortex of the brain that received the editing machinery showed a gene edit.

“The gene editing field largely agrees that, moving into the future, gene editing machinery should ultimately be delivered as proteins to minimize potential side effects and we’ve now shown an effective way to do that,” said Liu. “We plan to continue to actively work on improving eVLPs and adapting the technology to target other tissue types within the body.”

 

Funding:

Support for the study was provided in part by the National Institutes of Health, the Bill and Melinda Gates Foundation, the Howard Hughes Medical Institute, Foundation Fighting Blindness, the UC Irvine School of Medicine Dean’s office, a Research to Prevent Blindness unrestricted grant, and a National Science Foundation Graduate Research Fellowship.

Paper cited:

An, M. et al. Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo. Nature Biotechnology. Online January 8, 2024. DOI: 10.1038/s41587-023-02078-y 

 

About Broad Institute of MIT and Harvard

Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

 

Founded by MIT, Harvard, Harvard-affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide.

 

---

JOURNAL

Nature Biotechnology

DOI

10.1038/s41587-023-02078-y 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo

ARTICLE PUBLICATION DATE

8-Jan-2024

UK

Lancaster University leads NIHR study into improving community initiatives to empower residents

Peer-Reviewed Publication

LANCASTER UNIVERSITY

 

IMAGE: 

THE STUDY HAS INVESTIGATED THE HEALTH AND SOCIAL IMPACTS OF BIG LOCAL WITH THE AIM OF IMPROVING THE DEVELOPMENT OF FUTURE COMMUNITY INITIATIVES

view more 

CREDIT: STFC DARESBURY LABORATORY

Lancaster University has led on a major research project to help evaluate the impact of a large scale initiative in England – Big Local – that aimed to increase the control communities have over improvements in their neighbourhoods.

Funded by the National Lottery, Big Local began in 2010 with 150 areas where local residents were given £1 million over ten years to improve their own neighbourhood.

Residents had complete control over decisions about how the money was spent, with support from an independent organisation, Local Trust.

The £3M+ Communities in Control study from 2014 to 2021 is the longest evaluation of a community empowerment initiative ever conducted. The study has investigated the health and social impacts of Big Local with the aim of improving the development of future community initiatives.

As part of the study published in Public Health Research, researchers investigated how funding has acted as a facilitator for local action, as well as the challenges associated with community decision making. The study calculated that the original National Lottery grant of over £196M for the Big Local provided a return on investment of 30%.

They found “tentative evidence” that the mental health of populations in Big Local populations improved and burglaries were reduced.  There were also significant improvements in the mental health of residents actively involved in Big Local.

However, there was also evidence of negative impacts on health and wellbeing. Moreover, the benefits were also unequally distributed. Men were more likely than women to report improved mental wellbeing as were those with higher educational qualifications.

The third phase of the evaluation received over £700,000 from the NIHR Public Health Research Programme with earlier phases funded by the NIHR School for Public Health Research.

Led by Jennie Popay, Professor of Professor of Sociology and Public Health in the Division of Health Research, other Lancaster University researchers included Dr Emma Halliday, Dr Rebecca Mead, Dr Katharina Janke, Dr Michelle Collins, Dr Anne Townsend and Dr Joanna Reynolds and Professor Bruce Hollingsworth

Partner universities included Professor Margaret Whitehead from Liverpool, Professor Claire Bambra from Newcastle/Durham and Professor Matt Egan from Liverpool School of Hygiene and Tropical Medicine.

Professor Popay said: “Our findings on the positive and potential negative impacts on residents of place-based empowerment initiatives in relatively disadvantaged areas are particularly timely with growing calls in England for a new “community power paradigm” and the anticipated proposal of Government Levelling Up policies that may extend current policies, devolving more decision-making and resources down to local people.”

Matt Leach, chief executive of Local Trust, said: "Empowering residents to take the lead can drive substantial positive change. Future governments must prioritise communities at the heart of their policies if we are to address contemporary challenges effectively. 

“Communities across England are diverse and require tailored approaches. By offering appropriate resources, flexible long-term funding, and the means for local residents to form partnerships, these communities can effectively address and overcome these challenges. 

"This report demonstrates that just 10 years into what is a 15-year programme, National Lottery Community Fund investment in Big Local has delivered significant returns to local communities above and beyond the funds originally committed."

The study has implications for the design of future community empowerment initiatives, finding that:

• investment is needed to develop and sustain smaller scale community associations and organisations to emerge from and work with communities
• residents should take the lead in designing solutions but not necessarily be leaders in action
• local agencies should prioritise working as equal partners with communities rather than leaving communities to act alone.
• externally determined governance standards may undermine the development of communities’ capabilities for collective control

 

---

JOURNAL

Public Health Research

DOI

10.3310/GRMA6711 

METHOD OF RESEARCH

Case study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Investigating health and social outcomes of the Big Local community empowerment initiative in England

Adolescent sports activities help improve bone health in older adults, new study finds

Researchers examine the association between sports played during adolescence and bone mineral density at old age

Peer-Reviewed Publication

JUNTENDO UNIVERSITY RESEARCH PROMOTION CENTER

 

IMAGE: 

RESEARCHERS FROM JUNTENDO UNIVERSITY IN JAPAN SHOW THAT OLDER ADULTS WHO HAD ENGAGED IN HIGH-IMPACT SPORTS DURING THEIR ADOLESCENT YEARS INCUR LONG-TERM BENEFITS IN TERMS OF BONE HEALTH AND ENHANCED BONE MINERAL DENSITY.

view more 

CREDIT: YOSHIFUMI TAMURA FROM JUNTENDO UNIVERSITY, JAPAN

Loss of bone mineral density (BMD) with age is an important cause of osteoporosis (deterioration of bone tissue), which has been reported as one of the leading causes of falls among older adults in Japan. This leads to fractures that require long-term nursing. Prevention of osteoporosis in the aging population can thus help decrease the burden of disease and healthcare costs substantially.

 

Early lifestyle habits can largely influence health and disease onset in old age. In this regard, physical activities pursued during adolescent years can go a long way in preserving long-term health. These effects can be largely attributed to the gain of bone mass, which peaks during the 20s, and subsequently begins to decline with age. Notably, studies have shown that a 10% increase in peak bone mass during adolescence can delay osteoporosis by up to 13 years. However, which types of adolescent sports activities played during junior high and high school years have a positive impact on BMD and bone health in older adults is not known.

 

To bridge this gap, a team of researchers from Juntendo University, Japan, recently examined the relationship between the type of sport played during adolescence, together with individual-specific features, and BMD in old age. The study, published in Volume 14 of Frontiers in Physiology on 12 October 2023, was conducted by Professor Yoshifumi Tamura from the Faculty of International Liberal Arts, along with Ms. Hikaru Otsuka and Dr. Hiroki Tabata from the Sportology Center, Dr. Ryuzo Kawamori from the Department of Metabolism & Endocrinology, and Dr. Hirotaka Watada from the Department of Metabolism & Endocrinology at the Graduate School of Medicine.

 

Giving further insights into their findings, Prof. Tamura explains: “BMD is difficult to increase once it decreases. Therefore, it is important to increase peak bone mass during adolescence to maintain BMD in old age. Our study sheds light on the importance of exercise in adolescence for the prevention of osteoporosis and provides scientific evidence for establishing early preventive measures against osteoporosis in the future.”

 

The study included 1,596 older adults aged between 65 and 84 years, from the Bunkyo Health Study, residing in Bunkyo-Ku, an urban area in Tokyo, Japan. The researchers evaluated their physical fitness, blood biomarker levels including vitamin D, and BMD of the femoral neck (upper region of the thigh bone) and lumbar spine (lower region of the spine) regions using dual-energy X-ray absorptiometry. Further, the subjects were interviewed to assess their participation in sports activities during their adolescence. Other parameters, including comorbidities, lifestyle habits, medical history, and current medication status, were also recorded for analysis.

 

The researchers noted that while femoral neck and lumbar spine BMD values were in the normal range for men, women had lower values for them, with a larger number taking osteoporosis medication. Conversely, diabetes, physical activity, current smoking, and alcohol intake were significantly higher in men. The most common adolescent sports activities included baseball/softball, basketball, judo, table tennis, tennis, volleyball, and swimming.

 

The study found that basketball was associated with significantly high femoral BMD in older men and women. Further, body weight and serum vitamin D levels were found to influence femoral BMD. On the contrary, women who participated in volleyball and swimming had a higher lumbar spine BMD. However, sports type was not associated with lumbar spine BMD in older men. Notably, body weight, serum vitamin D, and presence of diabetes, were found to influence lumbar spine BMD.

 

Overall, these findings suggest that older adults who engaged in high-impact sports activities in their adolescence experience enhanced BMD and bone health in their old age. Moreover, the researchers emphasize that BMD benefits are not only limited to athletes but also extend to those in the general population who had indulged in physical activities at junior high and high school.

 

An early sport activity, once pursued as a hobby, can very well lay the foundation for lifelong healthy bones. Considering the long-term impact on the health of older adults, high-impact sports activities which stimulate bone growth should thus be encouraged in junior and high schools.

 

“Physical exercise in adolescence affects BMD more than 50 years later in older adults. Our findings can guide the selection of sports played during adolescence for longer health benefits,” concludes Prof. Tamura.

 

 

Reference

 

Authors	Hikaru Otsuka1,2, Hiroki Tabata1*, Huicong Shi1,2, Mari Sugimoto2, Hideyoshi Kaga3, Yuki Someya4, Hitoshi Naito3, Naoaki Ito3, Abulaiti Abudurezake1, Futaba Umemura2, Tsubasa Tajima3, Saori Kakehi1, Yasuyo Yoshizawa5, Muneaki Ishijima1,2,6, Ryuzo Kawamori1,2,3, Hirotaka Watada1,3, and Yoshifumi Tamura1,2,3,5,7*
Title of original paper	Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study
Journal	Frontiers in Physiology
DOI	10.3389/fphys.2023.1227639
Affiliations	1Sportology Center, Graduate School of Medicine, Juntendo University 2Department of Sports Medicine and Sportology, Graduate School of Medicine, Juntendo University 3Department of Metabolism and Endocrinology, Graduate School of Medicine, Juntendo University 4Graduate School of Health and Sports Science, Juntendo University 5Department of Healthy Life Expectancy, Graduate School of Medicine, Juntendo University 6Department of Medicine for Orthopaedics and Motor Organ, Graduate School of Medicine, Juntendo University 7Faculty of International Liberal Arts, Juntendo University

 

 

 

About Professor Yoshifumi Tamura

Yoshifumi Tamura, MD, PhD, is currently a Professor at the Faculty of International Liberal Arts at Juntendo University, Japan. He received an MD and PhD from Juntendo University in 1997 and 2005, respectively. He served as a Counselor at the Japan Sports Agency from 2016 to 2018. His research interests include insulin resistance, clinical diabetology, exercise therapy, obesity, and sarcopenia among others. He has over 200 publications to his name in these research areas, which have been cited more than 4,000 times.

 

 

Additional information for EurekAlert
Latest Article Publication Date:	12 October 2023
Method of Research:	Observational study
Subject of Research:	People
Conflicts of Interest Statement:	The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

 

---

DOI

10.3389/fphys.2023.1227639 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Frontiers in Physiology

FUNGI FUN

Finding a home for the wandering mushrooms —— Phylogenetic and taxonomic updates of Agaricales

Peer-Reviewed Publication

TSINGHUA UNIVERSITY PRESS

 

IMAGE: 

THE AGARICALES WAS DIVIDED IN TO 10 SUBORDERS. PHYLLOTOPSIDINEAE AND SARCOMYXINEAE ARE PROPOSED AS NEW SUBORDERS IN THIS STUDY.

view more 

CREDIT: GENG-SHEN WANG, KUNMING INSTITUTE OF BOTANY, CHINESE ACADEMY OF SCIENCES

Many edible, medicinal, and poisonous mushrooms that we are familiar with belong to the order Agaricales, which is a group of fungi with important economic and ecological value. Understanding the phylogenetic relationships of Agaricales can help us to know their evolutionary history and diversity, as well as their interactions with other organisms. Moreover, the phylogenetic framework of Agaricales can provide a basis for conserving biodiversity, such as measuring phylogenetic diversity and assessing the uniqueness and importance of different species.

 

Previous studies divided Agaricales into 8 suborders and 46 families, but the systematic position and phylogenetic relationship of some genera and species were unclear. For example, genera Tricholomopsis and Sarcomyxa have been controversial for a long time.

 

In collaboration with domestic and international colleagues, the research group of fungal diversity and molecular evolution at Kunming Institute of Botany, Chinese Academy of Sciences, conducted genome skimming of fungal specimens from the genera Tricholomopsis, Sarcomyxa, Macrotyphula, Phyllotopsis, and other related groups, and combined them with publicly available genome data of some other species of Agaricales from databases. Using various analytical methods, such as single-copy orthologous gene extraction, gene conflict detection, phylogenetic tree construction, and topology structure testing, they reconstructed the most resolved and robust phylogenetic framework of Agaricales based on the amino acid sequences of 555 single-copy orthologous genes, and clarified the phylogenetic relationships among suborders, as well as the systematic position of Tricholomopsis and Sarcomyxa. They proposed a new classification system of Agaricales with 10 suborders, and made some adjustments to the members of several suborders. They also formally published 2 new suborders (Sarcomyxineae and Phyllotopsidineae), 1 new genus (Conoloma), 2 new sections, and 6 new species, and solved many problems in the classification of Tricholomopsis in China. They also discussed the substrate preference and cap surface scale evolution of this genus.

 

“It has important scientific significance for further understanding the phylogenetic relationships among the major groups of Agaricales”, Geng-Shen Wang said.

---

See the article:

Phylogenetic and taxonomic updates of Agaricales, with an emphasis on Tricholomopsis

---

About Mycology

Mycology —— An International Journal on Fungal Biology is a renowned international, peer-reviewed, open access journal that publishes all aspects of mycological research, sponsored by the Institute of Microbiology, Chinese Academy of Sciences and the Mycological Society of China. Since its inception in 2010, Mycology received strong support from mycologists around the world. By publishing cutting-edge research and facilitating collaborations, Mycology strives to advance the understanding and knowledge of mycology, while fostering innovative research and scientific discussions in the field.

---

JOURNAL

Mycology&#58 An International Journal on Fungal Biology

DOI

10.1080/21501203.2023.2263031 

A novel strategy for extracting white mycelial pulp from fruiting mushroom bodies

Researchers successfully extract mycelial fibers from fruiting bodies of mushrooms without destroying their microsized mycelial structures

Peer-Reviewed Publication

SHINSHU UNIVERSITY

 

IMAGE: 

RESEARCHERS FROM SHINSHU UNIVERSITY REPORT AN INNOVATIVE WAY OF OBTAINING BLEACHED WHITE MYCELIUM FIBERS FROM REISHI AND ENOKI MUSHROOMS WHILE PRESERVING THEIR MICROSCALE MYCELIAL STRUCTURES.

view more 

CREDIT: SATOMI TAGAWA FROM SHINSHU UNIVERSITY, JAPAN

Mycelial fibers, the fibrous cells found in fruiting mushroom bodies, have gained momentum as a sustainable material for making leather and packaging owing to their excellent formability. Recently, a team of researchers from Shinshu University, Japan, has found a simple way of obtaining mycelial fibers, called “mycelial pulp,” from fruiting mushroom bodies and bleaching them using sunlight while keeping their mycelial structures intact.

Every year, humans generate millions of tons of waste, and almost 38% of that waste ends up in a landfill. A significant portion of it is made up of plastic or petroleum-based materials that can neither decompose nor degrade with time. This has led scientists to develop materials that are effective yet good for the environment.

One such alternative and renewable resource is mushroom-based materials. The root-like fruiting bodies of mushrooms, also known as mycelial fibers, have shown promising results as the new age, eco-friendly material for a wide range of consumer and industrial applications. The mycelium fibers from the fruiting body contain proteins, chitin, and polysaccharides, which make them ideal for making packaging materials, soundproofing, textiles, and much more. They are not only versatile but also have low environmental impact, are biodegradable, and have a low cost of production. However, conventional chemical or mechanical treatments used to obtain mycelium fibers have notable shortcomings. Many extraction processes tend to give the materials an unwanted color and often destroy their intricate mycelial structures, thereby limiting their nanoscale applications.

Now, a recent ACS Sustainable Chemistry & Engineering paper, made available online on 21 October 2023 and published on 6 November 2023, provides a simple and effective way of obtaining mycelial pulp and fibers from mushrooms without destroying their structure.

“Mushrooms, previously known primarily as a food resource, will now be utilized in everyday household items, allowing people to choose products that are safe, reliable, and environmentally friendly,” says Assistant Professor Satomi Tagawa from the Faculty of Engineering at Shinshu University, who led this study.

Dr. Tagawa and her team members, Dr. Hiroya Nakauchi, recipient of the Research Fellowship for Young Scientists of Japan Society for the Promotion of Science (JSPS) and Dr. Yoshihiko Amano, Professor at the Faculty of Engineering at Shinshu University, present a novel way of extracting the fibers which ensures that the mycelial structures remain intact.

The team treated the fruiting bodies of enoki mushrooms and the inedible reishi mushrooms with sodium hydroxide and hydrogen peroxide. They then bleached (or decolorized) the obtained substances by exposing them to sunlight. The now white material was subjected to ultrasonic treatment to defibrillate the pulp at a mycelial level. This process produced a dispersion containing micrometer-sized mycelium fibers with intact mycelial structures, as verified by Fourier-transform infrared spectroscopy.

The fibers obtained via this process showed excellent deformability and could be used for designing products like 3D porous sponges, 2D films, and 1D yarns.

Apart from obtaining a versatile mushroom-based material, this simple approach makes a valuable addition to the scrap-and-build approach for fabricating mushroom materials, which can complement the existing bottom-up approaches. “This technology has opened possibilities for upcycling unwanted by-products generated by the mushroom industry and making mushroom materials more circular and easier to reuse. We believe that further research on such sustainable materials and methods could create new industries, provide employment opportunities, and revitalize local communities,” remarks Dr. Tagawa, highlighting the scientific and social impact of their findings.

We hope that this research will help reduce waste on our planet and promote the bioeconomy!

 

###

 

About Shinshu University

Shinshu University is a national university founded in 1949 and located nestled under the Japanese Alps in Nagano known for its stunning natural landscapes. Our motto, "Powered by Nature - strengthening our network with society and applying nature to create innovative solutions for a better tomorrow" reflects the mission of fostering promising creative professionals and deepening the collaborative relationship with local communities, which leads to our contribution to regional development by innovation in various fields. We’re working on providing solutions for building a sustainable society through interdisciplinary research fields: material science (carbon, fibre and composites), biomedical science (for intractable diseases and preventive medicine) and mountain science, and aiming to boost research and innovation capability through collaborative projects with distinguished researchers from the world. For more information visit　https://www.shinshu-u.ac.jp/english/ or follow us on X (Twitter) @ShinshuUni for our latest news.

---

JOURNAL

ACS Sustainable Chemistry & Engineering

DOI

10.1021/acssuschemeng.3c04795 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Preparation of Mycelium Pulp from Mushroom Fruiting Bodies

ARTICLE TITLE

Phylogenetic and taxonomic updates of Agaricales, with an emphasis on Tricholomopsis

A high-tech research clinic on wheels

NHLBI study assesses health of residents in rural South for heart, lung disease

Peer-Reviewed Publication

NIH/NATIONAL HEART, LUNG AND BLOOD INSTITUTE

Adults in the rural South region, which includes Appalachia and the Mississippi Delta, have some of the highest rates of heart disease, obesity, high blood pressure, and chronic obstructive pulmonary disease (COPD) in the country. Heart failure rates, for example, are 19% higher in the rural South than in urban areas, while COPD rates are twice as high. It takes a toll as rural residents tend to live shorter lives, compared with urban residents.

No one knows exactly why the disease rates are so high, but researchers supported by the NHLBI are determined to find out.

Since 2021, they have been conducting the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study, a long-term research project aimed at uncovering the roots of these disparities. The researchers hope their findings will lead to actions and policies that help improve the health of the estimated 45 million people living in the region, which includes some of the poorest and most remote areas of the country.

In fact, it can take hours to reach health care in some parts of the region, for example.

To address this problem, the RURAL researchers have come up with a unique solution: They’ve built a state-of-the-art mobile exam unit, or MEU, that will bring to the region badly needed health technologies that make it possible for researchers to get the information they need. The MEU is basically a massive tractor-trailer -- about 52 feet long and weighing 53,000 pounds (26.5 US tons) – with the functionality of an urban primary care office. The custom-made unit houses a high-tech medical imaging room, examination room, laboratory, and waiting room.

David C. Goff, M.D., Ph.D., director of the NHLBI’s Division of Cardiovascular Sciences, said there’s great value in a study like this. “We know a lot about the health of urban populations, but there is a critical gap in research data regarding the health of people in the rural South that needs to be addressed,” he said. “In particular, we’d like to help reduce the region’s high burden of heart and lung diseases, the number one and number six leading causes of death in this country. The RURAL study is an important step toward that goal.”

“This is one of the first epidemiological cohort studies of its kind conducted in the rural South,” said Vasan Ramachandran, M.D., a co-leader of the RURAL Cohort Study and a professor and dean of the School of Public Health at the University of Texas Health Science Center at San Antonio. 

According to Ramachandran, the region’s health decline first became noticeable in the 1980s, and it has steadily worsened. Researchers think they know at least some of what’s contributing to the decline: vast food insecurity, poor access to healthcare, excess weight, and high rates of smoking. But they have had difficulty studying the area in detail – and broadly – due in part to its remoteness and lack of research infrastructure. The vehicle is scheduled to travel through 10 rural counties in Alabama, Kentucky, Louisiana, and Mississippi to conduct a variety of health exams on adult residents ages 25 to 64 who volunteer for the study. Already it’s been to four counties (two in Alabama and two in Mississippi), and about 2,100 participants, roughly half the study’s goal of 4,600 enrollees, have been tested.

Researchers have been looking at routine measures like blood pressure, cholesterol, and blood sugar levels, as well as images of the participants’ heart and lungs. They also have been administering surveys focused on the social determinants of health – the conditions in which people grow up, live, work, and play. Those include questions about education levels, income, neighborhoods, social stresses, and lifestyle, all of which give researchers insights they would never get from health exams alone. 

“So far, we’re seeing striking health challenges, including heart disease at a younger age, as well as high rates of obesity,” said Ramachandran, a former principal investigator for the NHLBI’s Framingham Heart Study, which has followed over 14,000 people since 1948. “Diseases that we saw in participants of the Framingham Heart Study at age 75 are occurring in these rural populations at age 50.” 

While it’s too early to publish comprehensive results from the study, some initial results might be published in early 2024, he said. Data collected by the researchers will be shared with the participants, who will be encouraged to share the information with their healthcare providers. If they do not have a provider, the researchers will refer them to local healthcare professionals. Some health data also will be shared with County officials to help them design improved healthcare policies and programs for the region.

“One of the keys to the success of our project is building up community trust, and we’re doing that by working closely with local community leaders,” Ramachandran said. “The community has welcomed us, and we hope this study will serve as a call to action to improve rural health in the South.”

The study, which is funded through 2025, involves a collaboration with over 50 investigators at 15 institutions nationwide. Researchers hope it will be renewed so they can re-examine the participants during a second visit and see how the diseases have progressed or whether improvements have occurred.

---

JOURNAL

Hypertension