Publisher Health

Scientists at the Francis Crick Institute have found a new treatment target for CDKL5 deficiency disorder (CDD), one of the most common types of genetic epilepsy.
CDD causes seizures and impaired development in children, and medications are limited to managing symptoms rather than tackling the root cause of the disease. The disorder involves losing the function of a gene producing the CDKL5 enzyme, which phosphorylates proteins, meaning it adds an extra phosphate molecule to alter their function.
Following recent research from the same lab showing that a calcium channel could be a target for therapy for CDD, the team has now identified a new way to potentially treat CDD by boosting another enzyme’s activity to compensate for the loss of CDKL5.
In research published today in Molecular Psychiatry, the scientists studied mice that don’t make the CDKL5 enzyme. These mice show similar symptoms to people with CDD like impaired learning or social interaction.
The researchers first identified that CDKL5 is active in nerve cells in mice but not in another type of brain cell called an astrocyte. In the nerve cells, they measured the level of phosphorylation of EB2, a molecule known to be targeted by CDKL5, to understand what happens when CDKL5 isn’t produced.
Interestingly, even in mice that don’t produce CDKL5, there was still some EB2 phosphorylation taking place, which suggested that another similar enzyme must also be able to phosphorylate it.
By looking at enzymes similar to CDKL5, the researchers identified that one called CDKL2 also targets EB2 and is present in human neurons. In mice without both CDKL5 and CDKL2, the remaining EB2 phosphorylation almost fully dropped off.

The researchers concluded that, although most activity comes from CDKL5, about 15% is from CDKL2, and the remaining

A new King’s College London scanning study of 390 babies has shown distinct patterns between term and pre-term babies in the moment-to-moment activity and connectivity of brain networks.
Supported by Wellcome and the National institute of Health and Care Research (NIHR) Maudsley Biomedical Research Centre, this is the first study to analyse how the communication between brain areas changes moment-to-moment in the first few weeks of life.
Published in Nature Communications, the study also found that these dynamic patterns of brain connectivity in babies were linked to developmental measures of movement, language, cognition and social behaviour 18 months later.
Joint senior author, Dr Dafnis Batallé, Senior Lecturer in Neurodevelopmental Science at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London said:
“Although we know how influential brain connectivity is on development, we know little about the patterns of dynamic functional connectivity in early life, and how they link to the way our brains mature. By analysing brain scans from 390 babies, we have begun to identify different transient states of connectivity that could potentially provide insight into how the brain is developing at this age and what behaviours and functions these patterns are linked to as the baby grows older.”
There is increasing awareness that conditions such as ADHD, autism and schizophrenia have their origins early in life, and that the development of these conditions may be linked to neonatal brain connectivity and its fluctuations over time.
Researchers used state-of-the-art techniques to evaluate functional Magnetic Resonance Imaging (fMRI) data on 324 full term babies and 66 pre-term babies (born at less than 37 weeks gestation). They assessed how the connectivity changed moment-to-moment during the time the baby was in the scanner to provide a dynamic picture. Previous research with babies has always used a measure of connectivity averaged over time spent in the scanner.

Dr Lucas França, first author andAssistant Professor in Computer and Information Sciences at Northumbria University. said:
“These findings are a result of carefully adapting methodologies derived from the domains of computer science and physics, specifically employed to unveil the intricacies inherent to the human neonatal brain. When these methodologies are allied to advanced techniques to obtain unprecedented data like the one from the Developing Human Connectome Project, we have a unique opportunity to deepen our understanding of the largely unknown realm of brain dynamics in early life.”
The study used methods that tap into how the brain connectivity fluctuates: one method that considers connectivity patterns across the whole brain and one that considers patterns within different regions of the brain.
The study identified six different brain states: three of these were across the whole brain and three were constrained to regions of the brain (occipital, sensorimotor and frontal regions). By comparing term and pre-term babies the researchers showed that different patterns of connectivity are linked to pre-term birth, for example pre-term babies spent more time in frontal and occipital brain states than term babies. They also demonstrated that brain state dynamics at birth are linked to a range of developmental outcomes in early childhood.
Joint senior author, Professor Grainne McAlonan, Interim Director of NIHR Maudsley BRC and Professor of Translational Neuroscience at IoPPN, King’s College London said:
“This is a real step forward in the use of imaging techniques to investigate how brain activity is continually changing in early life and how this provides a platform to support subsequent developmental milestones in childhood. The difference between term and pre-term babies suggests that time spent in or outside the womb shapes brain development. We now need to try and find out if it is possible to use these insights to identify and help those who need some additional support.”
The data was sourced from The Developing Human Connectome Project (dHCP), which is led by King’s College London and funded by the European Research Council. It is providing high resolution magnetic resonance brain images from unborn and newborn babies to scientists worldwide to support a large number of world-leading research projects into brain development and cerebral or mental health disorders.
Professor David Edwards, Principal Investigator of dHCP and Head of Department of Perinatal Imaging and Health, King’s College London said: “This study shows the power of the large set of data acquired by the Developing Human Connectome Project, an open science programme funded by the European Research Council and led by King’s College London in collaboration with Imperial College London and the University of Oxford. The data are freely available to researchers who want to study human brain development.”

Based solely on driving behavior and head/gaze motion, the newly developed tool recognizes low blood sugar levels.
Low blood sugar levels (hypoglycemia) are one of the most dangerous complications of diabetes and pose high risk during cognitively demanding tasks requiring complex motor skills, such as driving a car. The utility of current tools to detect hypoglycemia is limited by diagnostic delay, invasiveness, low availability, and high costs. A recent study published in the journal NEJM AI provides a novel way to detect hypoglycemia during driving. The research was the work of LMU scientists in collaboration with colleagues from the University Hospital of Bern (Inselspital), ETH Zurich, and the University of St. Gallen.
In their study, the researchers collected data from 30 diabetics as they drove a real car. For each patient, data was recorded once during a state with normal blood sugar levels and once during a hypoglycemic state. To this end, each patient was deliberately put into a hypoglycemic state by medical professionals present in the car. The collected data comprised driving signals such as car speed and head/gaze motion data — for example, the speed of eye movements.
Subsequently, the scientists developed a novel machine learning (ML) model capable of automatically and reliably detecting hypoglycemic episodes using only routinely collected driving data and head/gaze motion data. “This technology could serve as an early warning system in cars and enable drivers to take necessary precautions before hypoglycemic symptoms impair their ability to drive safely,” says Simon Schallmoser, doctoral candidate at the Institute of AI in Management at LMU and one of the contributing researchers.
The newly developed ML model also performed well when only head/gaze motion data was used, which is crucial for future self-driving cars. Professor Stefan Feuerriegel, head of the Institute of AI in Management and project partner, explains: “This study not only showcases the potential for AI to improve individual health outcomes but also its role in improving safety on public roads.”

A new study by researchers at University of Limerick in Ireland and at Iowa State University has demonstrated the impact resistance exercise training can have in the treatment of anxiety and depressive symptoms.
The new study provides evidence to support the benefits of resistance exercise training can have on anxiety and depression and offers an examination of possible underlying mechanisms.
The research, published in the Trends in Molecular Medicine journal, was carried out by Professor Matthew P Herring at University of Limerick and Professor Jacob D Meyer at Iowa State University.
The researchers said there was “exciting evidence” that resistance exercise training may be an accessible alternative therapy to improve anxiety and depression like more established therapies, while also improving other important aspects of health.
Dr Herring explained: “Anxiety and depressive symptoms and disorders are prevalent and debilitating public health burdens for which successful treatment is limited.
“The healthful benefits of resistance exercise training, or muscle-strengthening exercise involving exerting force against a load repeatedly for the purpose of generating a training response, are well-established,” said Dr Herring, Associate Professor in the Physical Activity for Health Research Centre, Health Research Institute, and Department of Physical Education and Sport Sciences within the Faculty of Education and Health Sciences in UL.
“However, the potential impact of resistance exercise training in the treatment of anxiety and depressive symptoms and disorders remains relatively understudied. Moreover, the plausible psychobiological mechanisms, which help us to better understand how and why resistance exercise training may improve these mental health outcomes, are poorly understood.”
The researchers argue that, while the available studies in this area are focused on relatively small sample sizes, there is sufficient evidence from previous and ongoing research at UL and the National Institute of Health funded research with Dr Meyer and colleagues at Iowa State University, to suggest that resistance exercise training does improve anxiety and depressive symptoms and disorders — though disorders themselves are scarcely studied.

“There is a critical need for confirmatory, definitive trials that adequately address limitations, including small sample sizes, but the limited evidence available to us provides initial support for the beneficial effects of resistance exercise training on these mental health outcomes, including increased insulin-like growth factor 1, cerebrovascular adaptations, and potential neural adaptations influenced by controlled breathing inherent to resistance exercise,” Dr Herring explained.
“We are tremendously excited to have what we expect to be a highly cited snapshot of the promising available literature that supports resistance exercise training in improving anxiety and depression.
“Notwithstanding the limitations of the limited number of studies to date, there is exciting evidence, particularly from our previous and ongoing research of the available studies, that suggests that resistance exercise training may be an accessible alternative therapy to improve anxiety and depression.
“A more exciting aspect is that there is substantial promise in investigating the unknown mechanisms that may underlie these benefits to move us closer to maximizing benefits and to optimising the prescription of resistance exercise via precision medicine approaches,” Dr Herring added.
Professor Meyer, a co-author on the study, said: “The current research provides a foundation for testing if resistance training can be a key behavioural treatment approach for depression and anxiety.
“As resistance training likely works through both shared and distinct mechanisms to achieve its positive mood effects compared to aerobic exercise, it has the potential to be used in conjunction with aerobic exercise or as a standalone therapy for these debilitating conditions.
“Our research will use the platform established by current research as a springboard to comprehensively evaluate these potential benefits of resistance exercise in clinical populations while also identifying who would be the most likely to benefit from resistance exercise.”

A new pharmacological inhibitor can intervene in a central cell death mechanism that is responsible for the death of motor neurons and hence important for the progression of the motor neuron disease amyotrophic lateral sclerosis (ALS). A research team led by Prof. Dr Hilmar Bading, neurobiologist at Heidelberg University, examined a neuroprotective molecule that belongs to a novel drug class. It is able to inhibit the interactions of certain proteins and has been successfully tested in a mouse model of ALS and in brain organoids of ALS patients. “On the long road to an effective treatment for ALS patients, these findings from basic research may represent a significant step forward,” says Prof. Bading.
ALS is a degenerative disease of the nervous system particularly affecting and harmful to motor neurons. As the disease progresses, the nerve cells controlling voluntary muscle movement die. That leads to a progressive wasting of the muscles responsible for moving and speaking, but also for eating and breathing. To date, says Prof. Bading, there is no effective drug treatment for ALS patients, who in most cases die within two to five years after the diagnosis.
The FP802 molecule the Heidelberg scientists used in the study belongs to a new pharmacological class of drugs. These are “TwinF interface inhibitors,” which were discovered by Prof. Bading and his team at the Interdisciplinary Center for Neurosciences (IZN) of Heidelberg University. These inhibitors disrupt the physical interactions of two ion channel proteins, with the names NMDA receptor and TRPM4, which, due to a so-called protein pocket named “TwinF” by the Heidelberg scientists, form a protein-protein complex.
NMDA receptors are found on the cell surface of nerve cells and are present both in the synapses, the contact points between the nerve cells, and outside these contact points. They are activated by a biochemical messenger substance, the neurotransmitter glutamate. The stimulation of synaptic NMDA receptors in the brain contributes to learning and memory processes, as well as to protecting nerve cells. Outside the synapses, however, the activation of these receptors leads to a damaging of nerve cells and to their death. The team around Hilmar Bading investigated the reasons for this in a prior study. They found out that TRPM4 confers toxic properties to the extrasynaptic NMDA receptors in the brain. Together these two proteins form a “death complex,” which also plays a role in ALS.
The neuroprotective molecule FP802 binds to the TwinF protein pocket of TRPM4, blocks the contact areas of the interacting proteins, and thereby disrupts the fatal complex of NMDA receptors and TRPM4. The Heidelberg scientists have studied this new drug principle using an ALS mouse model as well as brain organoids of ALS patients. “With this completely new therapeutic concept in combating neurodegenerative diseases we were able to achieve remarkable outcomes,” says Prof. Bading. The scientist explains that it was possible to prevent cell death and hence the loss of spinal motor neurons of mice by giving them the neuroprotectant. This treatment improved their motor abilities, mitigated the progression of the disease and extended the lifespan of the animals.
“The discovery of this new pharmacological class of drugs opens up a promising path for fighting ALS. A long-term goal is to develop TwinF interface inhibitors for use in patients,” says Hilmar Bading. In close cooperation with the startup FundaMental Pharma, a Biotech offshoot of the IZN Department of Neurobiology, the molecule FP802 is to be optimised for use in humans in the coming years and tested for efficacy in clinical trials. Dr Jing Yan, who was involved in the latest study, recently joined FundaMental Pharma in order to accelerate the further development of FP802.
The research was funded by the German Research Foundation, the European Research Council and the Alexander von Humboldt Foundation.

Using an old anesthesia drug to pull people out of the depths of severe depression has gone from fringe idea to widespread use in just a few years.
Sparked by promising studies and stories of lives transformed, clinics offering intravenous infusions of ketamine have popped up nationwide. Some also offer a newer, more expensive, nasal spray version.
But major questions remain about who ketamine can help, why some people get tremendous relief within days or weeks while others don’t, and the costs and benefits of different ways of delivering the drug.
New findings just came out from a study that seeks to answer some of those questions. They add more evidence about the power of IV ketamine to help some of the most severely ill people with depression or bipolar disorder who haven’t gotten relief from other treatments — including many who have frequent suicidal thoughts.
Called Bio-K, the study involved 74 people treated at four clinics in Michigan, Maryland and Minnesota. After just three infusions of ketamine over 11 days, 52% of participants saw their severe depression ease so much they achieved remission. Another 15% responded somewhat.
Half of those who had thought often of suicide before receiving ketamine experienced a dramatic drop in those impulses. The results are published in the Journal of Affective Disorders.
“These participants are very representative of the sickest patients we see, with more than 80% reporting suicidality that would have excluded them from other depression treatment studies,” said University of Michigan Health psychiatrist and study leader Sagar Parikh, M.D.

“As in other studies of ketamine, the initial response to treatment was a strong predictor of who would do well,” he added. “Two-thirds of those who responded after one infusion went on to achieve remission, while those who hadn’t responded measurably after two infusions were unlikely to start to respond after an additional one.”
Who responds and why?
Indeed, a third of all Bio-K participants didn’t respond to ketamine by the end of the three infusions provided under the study, leaving them to cope with one more failure in a series of attempted treatments.
The team’s in-depth interviews with some of these non-responders show how difficult that can be, as the team reported in a paper last year.
What’s the difference between them and those who responded? That’s a key focus of Bio-K, which is funded by donors to the U-M Eisenberg Family Depression Center.
By studying molecules in blood samples from the study’s participants, the Bio-K team hopes to find biomarkers that could predict who is most likely to get relief from ketamine, and who should try other options.

The study is evaluating cell signaling proteins, inflammatory markers and molecules that can indicate rates of cell metabolism in mitochondria. Early results from those analyses should be available in the next year.
From research to clinical use
In the meantime, the strength of the response in Bio-K participants helped fuel the founding of an IV ketamine clinic at University of Michigan Health, says Parikh, who oversees the clinic.
U-M now accepts referrals from providers across the region who have patients with treatment-resistant depression and need another option after trying at least four medications.
Patients come to the main U-M medical campus around eight times during the span of a month for infusions under the care of psychiatrists, anesthesiologists and other clinicians.
Parikh and his colleagues even wrote a guide for other hospitals on how best to set up and run such a clinic.
Who pays the cost?
Clinics like U-M’s work with health insurers that are willing to pay for some of the cost of ketamine therapy. But many patients pay some or all costs directly, or turn to Michigan Medicine’s financial support program, because insurance coverage varies widely including no coverage for people with Medicare or Medicaid.
That variation is partly because the intravenous form of ketamine doesn’t have an FDA approval specifically for treating depression, and no drug company can profit from seeking such an approval because the drug’s patent lapsed long ago.
In fact, Parikh and colleagues from around the country co-authored a recently published statement in the Journal of Affective Disorders on behalf of the National Network of Depression Centers, calling for more uniform insurance coverage of IV ketamine.
They note that half of all IV ketamine treatments at the network’s 24 centers are at least partly covered by insurance.
In addition to hospital based clinics, Parikh said there’s been a rise in commercial clinics where patients pay thousands of dollars of their own money for ketamine infusions and don’t even seek insurance coverage.
But that’s out of reach for many. And suppliers that are used to working with hospitals that use ketamine routinely for surgical sedation are growing warier of working with such independent clinics.
Parikh notes that his colleagues at the VA Ann Arbor Healthcare System offer IV ketamine treatment to veterans with coverage from the Veterans Health Administration. They recently published data showing encouraging responses in veterans nationwide and hope that more VA hospitals will start to offer it.
A newer version
Meanwhile, the nasal spray form of ketamine, called esketamine and sold under the name Spravato, has captured attention in recent years for its potential to ease disabling and life threatening symptoms without requiring an IV.
The spray involves a form of the drug manufactured by a pharmaceutical company in a way that isolates just one variety of the ketamine molecule, which allowed the company to seek a specific FDA approval.
Parikh notes that U-M was one of the sites for the original small study that led to Spravato’s approval by the FDA, and another larger study sponsored by Janssen, the drug’s manufacturer, that recently concluded. In addition to serving as the local principal investigator for these studies, Parikh also briefly served as a consultant to the company.
Based on the experience in these studies, U-M hopes to start offering Spravato alongside IV ketamine on a clinical basis. Even though it’s not given through an intravenous drip, the nasal spray still requires careful observation of patients under the FDA’s approval conditions.
IV vs nasal spray
Even as researchers search for biomarkers to predict ketamine response, clinicians find themselves with a conundrum: Which patients should start with IV ketamine, and which with Spravato? And how do the two compare head to head in actual response to treatment?
That’s what researchers at Yale University, U-M and their colleagues will soon try to find out, through a new study just funded by the federal Patient-Centered Outcomes Research Institute.
The study, which will begin enrolling up to 400 people at six sites nationwide later this year, will randomly assign people with treatment resistant depression to either the IV or nasal spray form of the drug. They’ll then receive that treatment for about four weeks, and have their symptoms monitored during treatment and for months afterward.
Such a head-to-head study might help inform insurers that haven’t yet started covering one or both forms of ketamine, Parikh noted.
More about the Bio-K results
In the meantime, the treatment response results from the Bio-K study and other studies can help more patients and clinicians understand the impact of IV ketamine.
Bio-K involves U-M, Johns Hopkins University and the Mayo Clinic, as well as the Pine Rest Christian Mental Health Services in western Michigan. It’s funded by a donation to the Eisenberg Family Depression Center in honor of its founding director John Greden, M.D., and coordinated through the National Network of Depression Centers.
Although Bio-K accepted people who were suicidal, which many antidepressant medication studies do not, it did not include people who use cannabis or those who have an active substance use disorder, schizophrenia or psychosis. But participants had to have failed to respond to at least two antidepressant or mood stabilizing medications after at least eight weeks, or failed to respond to six sessions of ECT, the treatment based on electric stimulation of the brain that has been seen as the last resort for many patients.
The study found that it did not matter if they got their infusions slowly over 100 minutes or in a standard session of 40 minutes.
At the start of the study, the average score of participants on a standard depression scale called MADRS was 28; that average dropped to 11 at 24 hours after the third infusion. A score of 10 or below is considered depression free, or remission, and a drop in score of at least 50% of the total score is considered response. In all, 67% achieved what is considered response, and 52% reached remission.

Contrary to popular belief, the benefits of physical activity do not outweigh the risks of cardiovascular disease associated with drinking sugar-sweetened beverages, according to a new study led by Harvard T.?H.?Chan School of Public Health. Jean-Philippe Drouin-Chartier, professor at Université Laval’s Faculty of Pharmacy, was a co-author.
Sugar-sweetened beverages are the largest source of added sugars in the North American diet. Their consumption is associated with a higher risk of cardiovascular disease, the world’s leading cause of death.
“The marketing strategies for these drinks often show active people drinking these beverages. It suggests that sugary drink consumption has no negative effects on health if you’re physically active. Our research aimed to assess this hypothesis,” says Drouin-Chartier.
For the study, the scientists used two cohorts totalling around 100,000 adults, followed for about 30 years. The data show that those who consumed sugar-sweetened beverages more than twice a week had a higher risk of cardiovascular disease, regardless of physical activity levels.
The study found that even if the recommended 150 minutes of weekly physical activity protects against cardiovascular disease, it’s not enough to counter the adverse effects of sugar-sweetened beverages. “Physical activity reduces the risk of cardiovascular disease associated with sugar-sweetened beverages by half, but it does not fully eliminate it,” says Drouin-Chartier.
The frequency of consumption considered in the study — twice a week — is relatively low but still is significantly associated with cardiovascular disease risk. With daily consumption, the risk of cardiovascular disease is even higher.
For this reason, Drouin-Chartier underlines the importance of targeting the omnipresence of sugar-sweetened beverages in the food environment. This category includes soft and carbonated drinks (with or without caffeine), lemonade, and fruit cocktails. The study did not specifically consider energy drinks, but they also tend to be sugar-sweetened.
For artificially sweetened drinks, often presented as an alternative solution to sugar-sweetened beverages, their consumption was not associated with higher risk of cardiovascular diseases. “Replacing sugar-sweetened beverages by diet drinks is good, because it reduces the amount of sugar. But the best drink option remains water,” explains Drouin-Chartier.
“Our findings provide further support for public health recommendations and policies to limit people’s intake of sugar-sweetened beverages, as well as to encourage people to meet and maintain adequate physical activity levels,” added lead author Lorena Pacheco, a research scientist in the Department of Nutrition at Harvard Chan School.

For some leukemia patients, the only potential chemotherapy option is a drug that also carries a high risk of heart failure. This means that some patients who recover from their cancer will end up dying of heart disease brought on by the cure.
In a new study, researchers from the University of Illinois Chicago and other universities have identified mechanisms that cause the drug, ponatinib, to harm the heart. They also identified a promising treatment that could reverse this process. The paper, with senior author Sang Ging Ong, assistant professor of pharmacology and medicine at UIC, is published in Circulation Research. The study is part of a growing field called cardio-oncology that investigates drugs that shrink tumors but can also cause heart problems.
While there are three options of drugs for treating chronic myeloid leukemia, many patients are resistant to the other two, leaving ponatinib as their only choice.
“These patients have no other options for treatment,” Ong said, despite the concerns about the drug’s side effects. In fact, ponatinib was pulled from the market for a few months after its introduction in 2012 because of concerns about heart problems.
The researchers were interested in understanding the interaction between ponatinib and the heart cells responsible for contraction. They discovered that ponatinib damages these cells by activating a process known as the integrated stress response.
The mechanism for this is related to the functioning of a kinase — an enzyme involved in energy transfer — called GCN2. The researchers found that ponatinib, despite being a kinase inhibitor, actually activates GCN2, which in turn switches on the integrated stress response. While this response isn’t always a bad thing — its purpose is to protect cells — it can also lead to their death under prolonged stress.
To see if this response was harming the cells, the researchers studied what would happen if they used a small molecule to block the integrated stress response in both cells and in mice during ponatinib treatment. They found that the treatment helped protect heart cells from the damaging side effects of the drug yet did not diminish ponatinib’s tumor-fighting efficacy.
“It protects the heart but at the same time, it still allows us to kill cancer cells,” Ong said.
More research is needed to know if this protective measure would work well in humans, Ong said. The mechanisms they identified are important in other cardiac diseases, as well, which could lead to future research on how to protect cells against different conditions.
Ong’s co-senior authors on the study are Won Hee Lee at the University of Arizona and Sang-Bing Ong at the Chinese University of Hong Kong. Other UIC authors at the College of Medicine or University of Illinois Cancer Center are Gege Yan, Zhenbo Han, Youjeong Kwon, Jordan Jousma, Sarath Babu Nukala, Xiaoping Du and Sandra Pinho, as well as Benjamin Prosser from the University of Pennsylvania.

In a study that signals potential reproductive and health complications in humans, now and for future generations, researchers from McGill University, the University of Pretoria, Université Laval, Aarhus University, and the University of Copenhagen, have concluded that fathers exposed to environmental toxins, notably DDT, may produce sperm with health consequences for their children.
The decade-long research project examined the impact of DDT on the sperm epigenome of South African Vhavenda and Greenlandic Inuit men, some of whom live in Canada’s North.
The study, published in the journal Environmental Health Perspectives, demonstrates a link between long-term exposure to DDT and changes in the sperm epigenome. These changes, particularly in genes vital for fertility, embryo development, neurodevelopment, and hormone regulation, correspond to increased rates of birth defects and diseases, including neurodevelopmental and metabolic disorders.
“We identified regions of the sperm epigenome that are associated with the serum levels of DDE (chemicals that form when DDT breaks down) and this association follows a dose-response trend. I think that’s quite striking, in that the more DDE you’re exposed to, the higher the chromatin, or DNA methylation defects are in the sperm,” said Ariane Lismer, PhD, the study’s lead author, who completed the work while pursuing her PhD at McGill’s Department of Pharmacology and Therapeutics.
“We demonstrate the sperm epigenome’s response to toxin exposures may be linked with disease in the next generation,” said Sarah Kimmins, PhD, who led the research as Professor of Pharmacology and Therapeutics at McGill and is also now a professor in the Department of Pathology and Cell Biology at Université de Montréal. “This is a critical new step for the field because while there are many studies of animals demonstrating toxin effects on the sperm epigenome, studies in humans have not comprehensively demonstrated this.”
Malaria, climate change, and the ‘grasshopper effect’
Despite a global ban on DDT to protect humans and the environment from its effects, the South African government has special permission to use it as an insecticide to control malaria. In some areas, home interiors are coated with the toxin. The study’s findings underscore the urgency to find alternative ways to control malaria and other vector-borne diseases.

“The reality is that people, especially young children and pregnant women, are still dying from malaria. We cannot afford for people in malaria-endemic regions to refuse spraying of their houses, as it will increase their risk of getting malaria,” says Tiaan de Jager, PhD, Dean of the Faculty of Health Sciences and Professor in Environmental Health at the School of Health Systems and Public Health at the University of Pretoria.
What’s more, the number of people and animals exposed to DDT is reportedly increasing due to climate change. DDT can travel vast distances through what is known as the ‘grasshopper effect,’ evaporating with warm air and returning to Earth with rain and snow in colder regions, where it persists in the Arctic food chain.
Rethinking fathers’ role in child development
The findings also highlight the importance of considering fathers in discussions about child health and development. While it’s commonly understood that women should avoid exposure to environmental contaminants during pregnancy, less attention has been given to how toxins affect fathers.
“We tend to think all fathers have to do is fertilize. But in fact, we forget that half of that genome and epigenome comes from the fathers, and half of it comes from the mothers. What that epigenome does in embryo development is critical for normal development,” says study co-author, Janice Bailey, PhD, formerly Professor of Animal Sciences at Université Laval and now the Scientific Director at Fonds de Recherche du Québec en Nature et Technologies (FRQNT).
Although the study focuses on DDT exposures, the researchers say it is not a leap to suggest that exposures to more common household endocrine disruptors such as those found in cosmetics and personal care items may act similarly.

The lifting of a two-decade drought in federal funding for firearm injury prevention research was strongly associated with an increase in both clinical trials and publications on gun violence, according to a new report published in JAMA Surgery.
For years, researchers interested in studying the causes, consequences, and prevention of firearm injury were stymied by severe restrictions on federal funding created by the passage of the Dickey Amendment in 1996.
That began to change in 2013, when the meaning of the Dickey Amendment was clarified. Small funds began to be awarded to researchers soon thereafter; and finally, in 2020, funds were reappropriated by the U.S. Congress to federal agencies like the National Institutes of Health (NIH) and U.S. Centers for Disease Control and Prevention (CDC) to increase scientists’ ability to rigorously study this growing public health epidemic.
According to the new report, from 2020 to 2022 (the time since congressional appropriations restarted), the CDC and NIH awarded approximately $49 million and $100.5 million, respectively, for firearm injury prevention research. The number of registered clinical trials and research publications increased in parallel — by 90% and 86%, respectively, from 2017-2019 to 2020-2022 — with a strong association between the amount of federal funding and the number of trials and publications.
The study, led by Dr. Megan L. Ranney, dean of the Yale School of Public Health, in collaboration with colleagues from Brown University, the University of Pennsylvania, and Yale School of Medicine, reviewed federal grants, registered clinical trials, and research publications related to firearm injury prevention in the U.S. between 1985 and 2022.
Of the total publications reviewed, 47% (869 articles) reported no funding; 16% (300 articles) were funded by the NIH; 11% (197 articles) by the CDC; and 38% (706 articles) by other sources such as private philanthropic organizations. The fact that many researchers published studies without federal funding support illustrates the motivational impact and compounding effect a robust federal funding environment can have on the science community, Ranney said.
“This study clearly shows that federal funding is a motivator and legitimator for investigators interested in firearm injury prevention,” Ranney said.
Most studies (55%) assessed community firearm violence; 48% of the studies focused on firearm suicides; and 21% investigated unintentional firearm injuries. Annual federal funding amounts positively correlated with the number of publications overall, the researchers said.
While the increase in scientific reports and intervention studies may partly be attributed to the current national gun violence crisis in the U.S., the role and impact of sustained federal funding in supporting firearm injury prevention research cannot be understated, Ranney said.
“This study shows that as rates of firearm injuries and death rise in the U.S., continued federal funding is critical for supporting and facilitating rigorous research and data-driven solutions,” said Ranney. “Research helps us understand what works and helps us invest our time and money in programs that will really make a difference. Already, CDC- and NIH-funded research has shown the value of some innovative new programs, such as the ‘See Something Say Something’ program. But more is needed.”