In utero exposure to tiny air pollution particles is linked to asthma in preschoolers

Mount Sinai researchers are first to find ultrafine particles from traffic pollution influences asthma risk in US children

THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

Research News

 

New York, NY (May 21, 2021) --Women who were highly exposed to ultra-fine particles in air pollution during their pregnancy were more likely to have children who developed asthma, according to a study published in the American Journal of Respiratory and Critical Care Medicine in May. This is the first time asthma has been linked with prenatal exposure to this type of air pollution, which is named for its tiny size and which is not regulated or routinely monitored in the United States.

Slightly more than 18 percent of the children born to these mothers developed asthma in their preschool years, compared to 7 percent of children overall in the United States identified as having asthma by the Centers for Disease Control and Prevention.

Other types of pollutants are routinely monitored and regulated to reduce potential health effects, such as larger-size particulate pollution and gaseous pollutants such as nitrogen dioxide. These have been associated with asthma risk in children in prior research. This study controlled for exposure to these other types of pollution and exposure to pollutants following birth, and it still found an elevated risk of asthma in children born to mothers with heightened exposure to ultra-fine particles in pregnancy.

Ultra-fine particulate pollution--particles that are smaller than the width of an average human hair--can get deeper into our lungs and pass into our circulation to cause various health effects. Because of this, the researchers said their toxic effects may actually be greater.

"One reason ultra-fine particulates are not routinely monitored is that there have been a number of unique challenges to measuring them accurately. Fortunately, recent methods have been developed to provide such exposure data which allowed us to conduct this study," said lead author Rosalind Wright, MD, MPH, Horace W. Goldsmith Professor in Children's Health Research, Professor of Environmental Medicine and Public Health and Co-director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai.

This study included 376 mothers and their children, most of them Black or Latinx, who live in the Boston metropolitan area and were already being followed to assess their health. Mount Sinai researchers partnered with a group of scientists at Tufts University in the Boston area who had developed a way to provide valid daily estimations of ultra-fine particulate exposure which could be linked to the area of the mothers' and children's homes. Many of these women were more likely to live near major roadways with higher traffic density where exposure to these tiny particles tends to be higher.

The researchers followed up with the mothers to find out whether the children were diagnosed with asthma. Most of the diagnoses of asthma occurred just after three years of age.

Pollution's effect in utero can alter lung development and respiratory health. This can lead to pediatric disorders like asthma. How this happens is not completely understood but pollution can alter certain bodily regulatory systems like neuroendocrine and immune function that have been linked with asthma in other studies.

While both boys and girls were affected by prenatal ultrafine particle exposure, this study found that girl babies were more sensitive to ultra-fine particle pollution's effects on asthma risk when exposed in late pregnancy. The reason for this phenomenon is also unclear, but studies show it is possibly due to endocrine-disrupting effects of the pollution exposure.

"This research is an important early step in building the evidence base that can lead to better monitoring of exposure to ultrafine particles in the United States and ultimately to regulation. As we advance methods for measuring these tiny particles, we hope for replication of these findings, both within different geographic areas across the United States as well as globally. Childhood asthma remains a global epidemic that is likely to grow with the anticipated rise in particulate air pollution exposures due to effects of climate change," Dr. Wright said.

###

This research was funded by grants from the National Institutes of Health including the Environmental Influences on Child Health Outcomes (ECHO) Program.

About The Institute for Exposomic Research

The Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai is the world's first research institute devoted to the intensive study of the exposome, or the totality of environmental influences on human health. The mission of the Institute is to understand how the complex mix of nutritional, chemical, and social environments affect health, disease, and development later in life and to translate those findings into new strategies for prevention and treatment. For more information, visit http://icahn.mssm.edu/exposomics.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care--from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

Russian wildfires and tropospheric ozone pollution over Northern Tibetan Plateau

INSTITUTE OF ATMOSPHERIC PHYSICS, CHINESE ACADEMY OF SCIENCES

Research News

 

IMAGE: BALLOON-BORNE MEASUREMENT OVER THE NORTHERN TP. view more 

CREDIT: JINQIANG ZHANG

Atmospheric ozone, which can regulate the amount of incoming ultraviolet radiation on the Earth's surface, is important for the atmospheric environment and ecosystems. Tropospheric ozone, primarily originating from photochemical reactions, is the third most prominent greenhouse gas causing climate warming.

A research team led by Dr. Jinqiang Zhang from the Institute of Atmospheric Physics (IAP) of the Chinese Academy of Sciences tried to analyze vertical ozone distributions and explore the influence of deep stratospheric intrusions and wildfires on ozone variation in the northern Tibetan Plateau (TP) during the Asian summer monsoon period.

Their findings were published in Atmospheric Research.

Ozone variation over the TP can influence weather and climate change. Unfortunately, surface observation sites on the northern TP are sparse due to the special terrain and harsh climate.

Ozonesonde, developed by the Key Laboratory of Middle Atmosphere and Global Environment Observation at IAP, was released over the northern TP in 2016, 2019, and 2020.

The researchers found that the deep stratospheric intrusion contributed to the occurrence of large ozone partial pressure in the troposphere.

"We also found that the large wildfire smoke occurring around central and eastern Russia in July 2016 caused ozone pollution in the troposphere over the northern TP, via long-range transport processes," said Dr. Dan Li, the corresponding author of the study.

The researchers warn that due to global warming, wildfires will increase and more pollution can be transported across China via long range.

###

RIGHT WING THINK TANK ECHOCHAMBER

A new replication crisis: Research that is less likely to be true is cited more

Papers that cannot be replicated are cited 153 times more because their findings are interesting, according to a new UC San Diego study

UNIVERSITY OF CALIFORNIA - SAN DIEGO

Research News

 

IMAGE: THE AVERAGE YEARLY CITATION COUNT PER YEAR FOR STUDIES THAT WERE NOT REPLICATED (ACCORDING TO P VALUE OF THE REPLICATION) IN EACH REPLICATION STUDY, AND FOR THOSE THAT WERE REPLICATED. THE... view more 

CREDIT: UC SAN DIEGO

Papers in leading psychology, economic and science journals that fail to replicate and therefore are less likely to be true are often the most cited papers in academic research, according to a new study by the University of California San Diego's Rady School of Management.

Published in Science Advances, the paper explores the ongoing "replication crisis" in which researchers have discovered that many findings in the fields of social sciences and medicine don't hold up when other researchers try to repeat the experiments.

The paper reveals that findings from studies that cannot be verified when the experiments are repeated have a bigger influence over time. The unreliable research tends to be cited as if the results were true long after the publication failed to replicate.

"We also know that experts can predict well which papers will be replicated," write the authors Marta Serra-Garcia, assistant professor of economics and strategy at the Rady School and Uri Gneezy, professor of behavioral economics also at the Rady School. "Given this prediction, we ask 'why are non-replicable papers accepted for publication in the first place?'"

Their possible answer is that review teams of academic journals face a trade-off. When the results are more "interesting," they apply lower standards regarding their reproducibility.

The link between interesting findings and nonreplicable research also can explain why it is cited at a much higher rate--the authors found that papers that successfully replicate are cited 153 times less than those that failed.

"Interesting or appealing findings are also covered more by media or shared on platforms like Twitter, generating a lot of attention, but that does not make them true," Gneezy said.

Serra-Garcia and Gneezy analyzed data from three influential replication projects which tried to systematically replicate the findings in top psychology, economic and general science journals (Nature and Science). In psychology, only 39 percent of the 100 experiments successfully replicated. In economics, 61 percent of the 18 studies replicated as did 62 percent of the 21 studies published in Nature/Science.

With the findings from these three replication projects, the authors used Google Scholar to test whether papers that failed to replicate are cited significantly more often than those that were successfully replicated, both before and after the replication projects were published. The largest gap was in papers published in Nature/Science: non-replicable papers were cited 300 times more than replicable ones.

When the authors took into account several characteristics of the studies replicated--such as the number of authors, the rate of male authors, the details of the experiment (location, language and online implementation) and the field in which the paper was published--the relationship between replicability and citations was unchanged.

They also show the impact of such citations grows over time. Yearly citation counts reveal a pronounced gap between papers that replicated and those that did not. On average, papers that failed to replicate are cited 16 times more per year. This gap remains even after the replication project is published.

"Remarkably, only 12 percent of post-replication citations of non-replicable findings acknowledge the replication failure," the authors write.

The influence of an inaccurate paper published in a prestigious journal can have repercussions for decades. For example, the study Andrew Wakefield published in The Lancet in 1998 turned tens of thousands of parents around the world against the measles, mumps and rubella vaccine because of an implied link between vaccinations and autism. The incorrect findings were retracted by The Lancet 12 years later, but the claims that autism is linked to vaccines continue.

The authors added that journals may feel pressure to publish interesting findings, and so do academics. For example, in promotion decisions, most academic institutions use citations as an important metric in the decision of whether to promote a faculty member.

This may be the source of the "replication crisis," first discovered the early 2010s.

"We hope our research encourages readers to be cautious if they read something that is interesting and appealing," Serra-Garcia said. "Whenever researchers cite work that is more interesting or has been cited a lot, we hope they will check if replication data is available and what those findings suggest."

Gneezy added, "We care about the field and producing quality research and we want to it to be true."

###

 

THE GNOMES OF ZURICH SPRACH

Missing role of finance in climate mitigation scenarios

UNIVERSITY OF ZURICH

Research News

 

Researchers at the University of Zurich show how climate mitigation scenarios can be improved by taking into account that the financial system can play both an enabling or a hampering role on the path to a sustainable economic system.

To limit global warming, a profound transformation of energy, production and consumption in our economies is required. The scale of the transformation means that the financial system must have a proactive role. New green investments are needed, as well as a reallocation of capital from high to low-carbon activities. The Central Banks and Supervisors Network for Greening the Financial System (NGFS), of which the Swiss National Bank is a member, was recently established with the aim of better understanding and managing the financial risks of climate change. The climate mitigation scenarios developed by the NGFS in collaboration with the Intergovernmental Panel on Climate Change of the United Nations (IPCC) have been a major step in providing financial actors with forward looking views on how low and high-carbon economic activities could evolve over the next decades. However, at this stage, these scenarios are based on large-scale Integrated Assessment Models (IAMs) that do not take into account the dynamic nature of the financial system and its actors. "We need to consider how the risk perception of the financial system from the scenarios can change the scenarios themselves," explains Stefano Battiston, professor at the Department of Banking and Finance at the University of Zurich.

Expansion of climate mitigation models

In their paper published in Science, Battiston and an international research group - with two authors being also authors of the upcoming IPPC Assessment Report - present a dynamic approach to complement climate mitigation scenarios. By describing what the world might look like in the coming decades, and being endorsed by financial authorities and large investors, climate mitigation scenarios have the power to change markets' expectations today. But this has an impact on the scenarios. "The economic system could go in the direction of the low-carbon transition, but it could also go the opposite way. It depends on what perception of risk the actors form from the scenarios," Battiston says. If investors find climate policies credible, they will adjust their expectations in a timely manner and reallocate capital to low-carbon investments early and gradually, which enables the transition to a more sustainable economy and a smoother adjustment of prices.

In contrast, investors could find the policies non-credible, delay revising their expectations, and do so later and in a sudden way. In particular, Battiston continues, "if financial actors collectively underestimate the risk of a late and sudden transition, the chance of this scenario materializing increases. This outcome could be a problem for financial stability and would therefore be more costly to society. It is thus also a concern for central banks and financial authorities. And it could lead to insufficient reallocation of capital into low-carbon investments. This is why it is so important."

Evaluate climate-financial risk and look at it dynamically

The authors of the study combine the current IAMs with a climate-financial risk assessment (CFR) in a circular way. In doing so, they show how the perception of the financial system and the timing of the introduction of climate policy measures interact in the low-carbon transition. The feedback loop map possible changes in investors' expectations and thus lead to more coeherent scenarios to assess climate-related financial risk.

The findings from the study have practical implications for the implementation of fiscal policy measures, and financial policy and regulation. They shed also new light on the discussion around the principle of "double materiality", which involves taking into account financial as well as non-financial opportunities and risks for financial firms.

###

Women’s Access to Abortion Care Under Oregon's Reproductive Health Equity Act

Maria I. Rodriguez, MD, MPH¹; Megan Skye, MPH¹; Mitra Shokat, BA²; et alRachel Linz, MPH³; Nisreen Pedhiwala, MPH³; Blair G. Darney, PhD, MPH^1,2

Author Affiliations Article Information

JAMA Health Forum. 2021;2(5):e210402. doi:10.1001/jamahealthforum.2021.0402

Research Letter

May 21, 2021

Introduction

Unintended pregnancy and abortion are becoming increasingly concentrated among women in disadvantaged communities who experience substantial barriers to obtaining health care.¹ A common barrier to accessing needed abortion care is cost, as more than half of all abortions are paid for out of pocket.² While no federal funds can be used for abortion, 16 states, including Oregon, use state funds to cover all or most abortions in Medicaid.³ However, federal law restricts access to Medicaid for undocumented and recent immigrants.⁴

Oregon’s Reproductive Health Equity Act (RHEA) took effect January 1, 2018, and ensured coverage for family planning (abortion and contraception) using state funds for all low-income state residents regardless of citizenship status. We describe the first 24 months of abortion services covered under RHEA and distances traveled by women to receive care.

Methods

We conducted a cross-sectional study of abortion services that were reimbursed under RHEA in 2018 and 2019. We used data from the program’s “Clinic Visit Record,” which includes demographic and medical information, as well as billing claims. This program is separate from the state’s Medicaid program. We included abortions that were reimbursed under RHEA at 11 clinics statewide that provide abortion services, with the exception of 1 hospital-based clinic. No hospital was contracted to provide scheduled abortion care during the study period. Emergency hospital-based abortions for life-threatening conditions (eg, hemorrhage) would be reimbursed by Medicaid and are not included in the study sample. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. The institutional review boards at Oregon Health & Science University and the Oregon Health Authority approved the study and granted a waiver of informed consent based on the lack of HIPPA identifiers.

We describe sociodemographic, clinical, and abortion characteristics of women who received abortions under RHEA by metropolitan residence (vs nonmetropolitan) based on zip code. Our primary outcome was the distance traveled to receive an abortion. We used the patient-reported zip code of residence to calculate the distance the patient traveled to receive an abortion using the straight-line distance between centroids of the patient’s zip code and the latitude and longitude of the clinic where the patient received an abortion. Statistical analyses were conducted using Stata, version 16 (StataCorp), and statistical significance was set at P < .05.

Results

Oregon’s RHEA provided access to 625 clinic-based abortions. Nearly half (302 [48.3%]) of the abortions were for women aged 25 to 34 years (range, 15-46 years). Most abortions (498 [79.7%]) were for women who resided in metropolitan zip codes. Consistent with national trends, most abortions (583 [93.9%]) occurred during the first trimester, and slightly more than half (358 [57.3%]) were surgical abortions.⁵ More than 509 abortions (80%) were performed for women who had previously given birth. There was no difference in rates of second trimester abortion by residence (5.6% metropolitan vs 6.3% nonmetropolitan; P = .94).

In the overall cohort, the median distance traveled for an abortion was 8.73 miles (interquartile range, 4.78-17.20 miles; range, 0.42-124.44 miles). A third of women (189 [30.2%]) traveled less than 5 miles to receive abortion care, and 32 (5.1%) traveled 50 or more miles.

Discussion

In the first 2 years following RHEA implementation, immigrant women across the state used the expanded coverage to access abortion, indicating that the policy was fully implemented in metropolitan and nonmetropolitan areas. The distances traveled for abortion in Oregon were lower than national averages (5.1% of RHEA clients vs 18% nationally traveling more than 50 miles).⁵ Our study is limited by the lack of information on abortions received by low-income immigrants before implementation of the RHEA policy and not including information on contraception. State policies, such as RHEA, can ensure that low-income individuals are not excluded from family planning services based on citizenship status.

Back to top

Article Information

Accepted for Publication: March 15, 2021.

Published: May 21, 2021. doi:10.1001/jamahealthforum.2021.0402

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Rodriguez MI et al. JAMA Health Forum.

Corresponding Author: Maria I. Rodriguez, MD, MPH, 3181 SW Sam Jackson Park Rd, UHN 50, Portland, OR 97239 (rodrigma@ohsu.edu).

Author Contributions: Drs Rodriguez and Darney had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rodriguez, Darney.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Rodriguez.

Critical revision of the manuscript for important intellectual content: Skye, Shokat, Linz, Pedhiwala, Darney.

Statistical analysis: Rodriguez, Skye, Shokat, Darney.

Administrative, technical, or material support: Rodriguez, Linz, Pedhiwala.

Supervision: Rodriguez, Darney.

Conflict of Interest Disclosures: Dr Rodriguez reported personal fees from the American Congress of Obstetrics and Gynecology, World Health Organization, and Bayer as well as grants from Merck, the National Institutes of Health, and Arnold Ventures outside the submitted work. No other disclosures were reported.

References

1.

Finer  LB, Zolna  MR.  Declines in unintended pregnancy in the United States, 2008-2011.   N Engl J Med. 2016;374(9):843-852. doi:10.1056/NEJMsa1506575PubMedGoogle ScholarCrossref

2.

Jerman  J  Jr, Onda  T. Characteristics of US abortion patients in 2014 and changes since 2008. Accessed May 8, 2019. https://www.guttmacher.org/sites/default/files/report_pdf/characteristics-us-abortion-patients-2014.pdf

3.

Guttmacher Institute. State funding of abortion under Medicaid. Accessed June 8, 2020. https://www.guttmacher.org/print/state-policy/explore/state-funding-abortion-under-medicaid

4.

DuBard  CA, Massing  MW.  Trends in emergency Medicaid expenditures for recent and undocumented immigrants.   JAMA. 2007;297(10):1085-1092. doi:10.1001/jama.297.10.1085
ArticlePubMedGoogle ScholarCrossref

5.

Kortsmit  K, Jatlaoui  TC, Mandel  MG,  et al.  Abortion surveillance—United States, 2018.   MMWR Surveill Summ. 2020;69(7):1-29. doi:10.15585/mmwr.ss6907a1PubMedGoogle ScholarCrossref

 #PHARMACARE NOW!

Providing medications for free leads to greater adherence and cost-savings, study shows

ST. MICHAEL'S HOSPITAL TORONTO CANADA

Research News

 

IMAGE: DR. NAV PERSAUD, A SCIENTIST AT THE LI KA SHING KNOWLEDGE INSTITUTE OF ST. MICHAEL'S HOSPITAL. view more 

CREDIT: UNITY HEALTH TORONTO

Free access to essential medicines increases patient adherence to taking medication by 35 per cent and reduces total health spending by an average of over $1,000 per patient per year, according to a two-year study that tested the effects of providing patients with free and convenient access to a carefully selected set of medications.

The findings, published May 21 in PLOS Medicine, come as advocates urge Canada to carve a path toward single-payer, public pharmacare. Canada is the only country with universal healthcare that does not have a universal pharmacare program.

A group of researchers led by St. Michael's Hospital of Unity Health Toronto recruited a total of 786 patients across nine primary care sites in Ontario who reported cost-related non-adherence to medications. Most of the study participants were recruited from St. Michael's Department of Family and Community Medicine and others were recruited from three rural sites. Participants were randomized into two groups - half received free medications via mail, the other half had their usual access to medications.

Two years into the study, adherence to all appropriate prescribed medicines was 35 per cent higher in the free distribution group compared with the group that had usual access to medications. Free distribution of medication also showed to reduce healthcare costs, including hospitalization, by an average of $1,222 per patient per year.

"The cost savings are substantial, but they are less important than people simply being able to afford taking lifesaving medications," said Dr. Nav Persaud, a scientist at the Li Ka Shing Knowledge Institute of St. Michael's and lead author of the study.

"This is the first study of providing people with free access to a comprehensive set of medicines, and hopefully it will be the last one needed before policy changes," said Dr. Persaud, who is also a family physician at St. Michael's Hospital.

In June 2019, the Advisory Council on the Implementation of National Pharmacare recommended a universal, single-payer, public pharmacare, estimating such a program would save Canada an estimated $5 billion per year. The report cited a list of medicines like the one used in the CLEAN Meds study as "a starting point" for determining which drugs all Canadians should have free access to.

The CLEAN Meds Trial focused on 128 essential medicines, adapted from the WHO Model List of Essential Medicines and removed treatments not needed in Canada. The medicines in the study included treatments for acute conditions, such as antibiotics and pain relievers, as well as chronic conditions, such as antipsychotics and HIV-AIDS medications.

The paper is the final result of the CLEAN Meds Trial. Preliminary results of the trial after one year of free medication indicated improved adherence, improvements in some health outcomes, and that free distribution of essential medicines led to a 160 per cent increase in the likelihood of participants being able to make ends meet.

###

PUBLIC OWNERSHIP OF BIG PHARMA

Nonprofits, federal government surpass pharma to lead Alzheimer's drug development

ALZHEIMER'S ASSOCIATION

Research News

 

Two articles published online today by Alzheimer's & Dementia: Translational Research & Clinical Interventions, a journal of the Alzheimer's Association, show substantial changes in the focus and funding of clinical trials for Alzheimer's disease therapies. The newly published articles throw a greater spotlight on a decision -- now before the U.S. Food and Drug Administration (FDA) -- that would potentially bring a new drug therapy to Alzheimer's patients for the first time in nearly 20 years.

Researchers analyzed clinicaltrials.gov, the U.S. National Library of Medicine's database, and five years of annual Alzheimer's pipeline reviews published by UNLV School of Integrated Health Sciences research professor Jeffrey L. Cummings and colleagues. The results capture the well-publicized retreat of pharma from Alzheimer's clinical trials, especially early phase human trials, and the emergence of federal agencies and nonprofit organizations as the primary drivers of growth and innovation.

In the first study, "Who Funds Alzheimer's Disease Drug Development?," Cummings and colleagues found that the number of Alzheimer's clinical trials supported by pharmaceutical companies has decreased over the past five years, while trials supported by federal government sources and public-private partnerships (PPP) have increased. The authors observe that pharma companies are not increasing their involvement in Alzheimer's trials and drug development except through PPP, enabling them to distribute the cost and risk. And they largely engage only in late-stage (Phase 3) clinical trials.

The researchers found that the trials gap is increasingly being filled by academic medical centers (AMCs). Trials by AMCs are up 78% over the past five years, primarily funded by the U.S. National Institutes of Health (NIH) and programs of the National Institute on Aging (NIA), Alzheimer's Association, and Alzheimer's Drug Discovery Foundation (ADDF), including the Alzheimer's Association's Part The Cloud initiative.

"Nonprofits and the NIH are making a huge difference in drug development for Alzheimer's and all other dementia," Cummings said. "Recent years have been a time of pharma retrenchment after multiple negative clinical trials, but also a time of innovation in early-stage trials and re-evaluation of previously under-resourced ideas. We found in our review that, in the newer early-stage clinical trials, the therapeutic mechanisms are more diversified, biomarkers are more regularly used, and repurposed agents are being explored -- increasingly led by academic researchers and funded by NIH, the Alzheimer's Association, and ADDF.

A second paper, "Alzheimer's Disease Drug Development Pipeline: 2021," also by Cummings and colleagues, including a student, Justin Bauzon, from the UNLV School of Medicine, reinforces these trends by showing that, despite pharma's retreat from Alzheimer's, the total number of agents in Alzheimer's clinical trials has been relatively steady over the last five years. The total is up slightly from 2020, driven by additional agents in Phase 2 studies. There is also increasing diversity of targets and therapeutic mechanisms of drugs in the Alzheimer's pipeline, driven by innovative Phase 1 and 2 trials.

"Alzheimer's Association funding, partnerships - including the NIA and ADDF - and advocacy for federal Alzheimer's research funding are now the primary drivers of growth in Alzheimer's clinical trials, filling the gap left by pharma's retreat, and growing and diversifying the front end of the drug pipeline," said Maria C. Carrillo, Alzheimer's Association chief science officer.

The NIA now distributes more than $3 billion annually for Alzheimer's and dementia research, up from $500 million just a few years ago. "This great victory is almost completely due to Alzheimer's Association legislative efforts, our grassroots advocates, and our champions in Congress," Carrillo said.

The FDA is reviewing aducanumab (Biogen) for the treatment of Alzheimer's disease. A decision is expected by June 7.

"If pharma companies do not see a clear path to FDA approval, they will continue not to invest in Alzheimer's," Cummings said. "This further highlights the importance of the decision before the FDA at this moment."

There are four drugs approved and commonly used to treat the symptoms of Alzheimer's dementia, plus a combination therapy that includes two of these drugs. There are currently no approved drugs that change the course or delay the progression of the disease or that delay or stop clinical decline. No new drugs have been approved for Alzheimer's since 2003.

The article authors say, "If new therapies are approved by regulatory authorities, more sponsors and more funding may be attracted to Alzheimer's research with accelerated innovation."

The two studies were supported by the Chambers-Grundy Center for Transformative Neuroscience at UNLV, dedicated to advancing clinical trial methods to get better treatments to patients faster.

###

UNLV Department of Brain Health

The UNLV Department of Brain Health was launched by the School of Integrated Health Sciences (SIHS) in 2019 to advance research, education, and practice to benefit brain health and the care and treatment of people with brain disorders. The department's faculty specialize in basic and clinical research in neurodegenerative disease, neuropsychology, and occupational therapy.

Alzheimer's & Dementia: Translational Research & Clinical Interventions (TRCI)

Alzheimer's & Dementia: TRCI is a peer-reviewed, open-access journal from the Alzheimer's Association that bridges the full scope of explorations between basic research, drug discovery, and clinical studies in Alzheimer's and dementia. The journal publishes findings from multifaceted domains of research and disciplines to accelerate what is learned at the bench and translated and applied at the bedside.

Can antibiotics treat human diseases in addition to bacterial infections?

UIC researchers prove that drugs designed for bacteria have potential to act on human cells

UNIVERSITY OF ILLINOIS AT CHICAGO

Research News

 

IMAGE: AN ANTIBIOTIC (GREEN), BOUND IN THE HUMAN-LIKE YEAST RIBOSOME (GRAY), ALLOWS FOR SYNTHESIS OF SOME PROTEINS (REPRESENTED IN ORANGE, PURPLE, AND BLUE) BUT NOT OTHERS (DARK GREEN). view more 

CREDIT: MAXIM SVETLOV/UIC

According to researchers at the University of Illinois Chicago, the antibiotics used to treat common bacterial infections, like pneumonia and sinusitis, may also be used to treat human diseases, like cancer. Theoretically, at least.

As outlined in a new Nature Communications study, the UIC College of Pharmacy team has shown in laboratory experiments that eukaryotic ribosomes can be modified to respond to antibiotics in the same way that prokaryotic ribosomes do.

Fungi, plants, and animals -- like humans -- are eukaryotes; they are made up of cells that have a clearly defined nucleus. Bacteria, on the other hand, are prokaryotes. They are made up of cells, which do not have a nucleus and have a different structure, size and properties. The ribosomes of eukaryotic and procaryotic cells, which are responsible for the protein synthesis needed for cell growth and reproduction, are also different.

"Some antibiotics, used for treating bacterial infections, work in an interesting way. They bind to the ribosome of bacterial cells and very selectively inhibit protein synthesis. Some proteins are allowed to be made, but others are not," said Alexander Mankin, the Alexander Neyfakh Professor of Medicinal Chemistry and Pharmacognosy at the UIC College of Pharmacy and senior author of the study. "Without these proteins being made, bacteria die."

When people use antibiotics to treat an infection, the cells of the patient are not affected because the drugs are not designed to bind to the differently shaped ribosomes of eukaryotic cells.

"Because there are many human diseases caused by the expression of unwanted proteins -- this is common in many types of cancer or neurodegenerative diseases, for example -- we wanted to know if it would be possible to use an antibiotic to stop a human cell from making the unwanted proteins, and only the unwanted proteins," Mankin said.

To answer this question, Mankin and study first author Maxim Svetlov, research assistant professor with the department of pharmaceutical sciences, looked to yeast, a eukaryote with cells similar to human cells.

The research team, which included partners from Germany and Switzerland, performed a "cool trick," Mankin said. "We engineered the yeast ribosome to be more bacteria-like."

Mankin and Svetlov's team used biochemistry and fine genetics to change one nucleotide of more than 7,000 in yeast ribosomal RNA, which was enough to make a macrolide antibiotic -- a common class of antibiotics that works by binding to bacterial ribosomes -- act on the yeast ribosome. Using this yeast model, the researchers applied genomic profiling and high-resolution structural analysis to understand how every protein in the cell is synthesized and how the macrolide interacts with the yeast ribosome.

"Through this analysis, we understood that depending on a protein's specific genetic signature -- the presence of a 'good' or 'bad' sequence -- the macrolide can stop its production on the eukaryotic ribosome or not," Mankin said. "This showed us, conceptually, that antibiotics can be used to selectively inhibit protein synthesis in human cells and used to treat human disorders caused by 'bad' proteins."

The experiments of the UIC researchers provide a staging ground for further studies. "Now that we know the concepts work, we can look for antibiotics that are capable of binding in the unmodified eukaryotic ribosomes and optimize them to inhibit only those proteins that are bad for a human," Mankin said.

###

Additional co-authors of the study are Dorota Klepacki and Nora Vázquez-Laslop of UIC; Timm Koller and Daniel Wilson of the University of Hamburg; Sezen Meydan and Nicholas Guydosh of the National Institutes of Health; and Norbert Polacek and Vaishnavi Shankar of the University of Bern.

This work was supported by grants from the National Institutes of Health (R35 GM127134, DK075132, 1FI2GM137845), the German Research Foundation (WI3285/6-1), and the Swiss National Science Foundation (31003A_166527).