Category: 8. Health

Aberrations in fibroblast growth factor receptors FGFR2/3 are major drivers of many cancers—including intrahepatic cholangiocarcinoma, endometrial, breast, gastric, and bladder cancers. However, the development of selective inhibitors targeted FGFR2/3 has long been challenged by the high sequence and structural similarity among FGFR family members, particularly the binding pocket homology among FGFR1, FGFR2, and FGFR3 exceeds 95%.

Currently approved pan-FGFR inhibitors lack selectivity and often inhibit FGFR1/4 as well, leading to dose-limiting toxicities such as hyperphosphatemia and diarrhea, reduced treatment efficacy. Compounding these challenges, the emergence of resistance-conferring mutations in FGFR2/3 frequently diminishes the effectiveness of current drugs.

To address this challenge, the Insilico team employed advanced molecular modeling techniques in combination with the company’s proprietary generative AI-based chemistry engine, Chemistry42, to efficiently design highly selective FGFR2/3 inhibitors featuring a novel core structure. This research, recently published in the Journal of Medicinal Chemistry , provides an innovative approach for the discovery and development of next-generation cancer therapies targeting FGFR2/3.

The process began with structural analysis and molecular modeling, which identified the hinge-binding region (core A) as a key contributor to FGFR2/3 binding. Based on these insights, the researchers defined a pharmacophore model that retained essential hydrogen bond donors and acceptors, as well as relevant features for selectivity and potency.

The Chemistry42 platform was then leveraged to generate a library of approximately 10,000 molecules with diverse core structures and linkers, prioritizing those predicted to exhibit strong protein-ligand interactions (as measured by PLI score) and favorable drug-like properties. Based on the generated amide-based scaffold, we found that flexible binding to the kinase hinge region can better accommodate various types of resistance mutations. By filtering for optimal molecular characteristics and high PLI scores, the team identified core3 (C3) as a structural motif likely to deliver high potency and selectivity for FGFR2/3.

Further ADMET prediction and Alchemistry—the free energy calculations module of Chemistry42—were subsequently used to rank and optimize the candidate molecules. This process ultimately led to the identification of ISM7594, a covalent dual FGFR2/3 inhibitor distinguished by its unique hinge-binding motif and novel core structure.

In the validation studies, ISM7594 exhibits nanomolar inhibitory activity against FGFR2 and FGFR3, with over 100-fold selectivity relative to FGFR1/4. It maintained strong efficacy against clinically relevant FGFR2/3 mutants associated with therapeutic resistance. In cancer cell lines harboring FGFR2/3 alterations, ISM7594 showed robust antiproliferative effects, while exhibiting minimal impact on cells without FGFR aberrations. In preclinical animal models, ISM7594 displayed favorable pharmacokinetic properties, significant tumor growth inhibition, and a reduced toxicity profile compared to less selective FGFR inhibitors.

“Our study not only demonstrates the speed and precision of AI-enabled drug design but also the importance of rigorous experimental validation to translate in silico discoveries into real, clinically relevant therapies,” said Xiao Ding, PhD, Head of Chemistry & DMPK and Senior Vice President of Medicinal Chemistry at Insilico Medicine.

In February 2025, Insilico published a research paper in the Journal of Medicinal Chemistry entitled “Discovery of Pyrrolopyrazine Carboxamide Derivatives as Potent and Selective FGFR2/3 Inhibitors that Overcome Mutant Resistance,” further demonstrating the process of core structure optimization for novel, highly selective FGFR2/3 inhibitors.

Since its founding in 2014, Insilico Medicine has published more than 200 peer-reviewed papers. Leveraging sustained scientific breakthroughs at the intersection of biotechnology, artificial intelligence, and automation, Insilico Medicine secured a position among the Top 100 global corporate institutions for biological sciences and natural sciences publications, and ranked 43rd among global corporate institutions in the USA across all-subject output.

Reference

[1] Wang, Y. et al. (2025) ‘Rational design and identification of ISM7594 as a Tissue-Agnostic FGFR2/3 inhibitor,’ Journal of Medicinal Chemistry [Preprint]. https://doi.org/10.1021/acs.jmedchem.5c00928 .

About Insilico Medicine

Two studies led by researchers at Imperial College London (ICL) have identified structural brain changes and blood biomarkers linked to dementia in former professional rugby players. 

The findings provide the first prospective evidence of physical brain and blood abnormalities in this group. 

Previous research had already shown that elite rugby players face a higher risk of neurodegenerative diseases later in life. The studies examined links between repeated head impacts in rugby and conditions such as Alzheimer’s disease and chronic traumatic encephalopathy (CTE).

Post-mortem examinations of former players have shown neuropathologies consistent with repetitive brain trauma.

Traumatic brain injury, already a known risk factor for neurodegeneration, contributes to an estimated 3%-15% of dementia cases in the general population.

While recent advances in fluid and imaging biomarkers have transformed dementia diagnosis, these techniques have not been systematically applied to rugby players previously exposed to multiple head impacts.

Study Cohort and Methods

The research involved 200 ex-professional rugby players aged 30 to 61 (median age, 44), all of whom had self-referred with brain health concerns but had no dementia diagnosis at baseline. At least one previous concussion while playing was reported by 193 (96.5%) of the former players, with a median of seven concussions.

The rugby group was compared with 33 age- and sex-matched healthy controls with no evidence of previous head trauma or dementia onset. 

Participants were 90% male. The median rugby career lasted 10.5 years, with 63% playing as forwards and 37% as backs.

Mental Health and Behavioural Symptoms

The former players scored higher on self-rated scales of depression, anxiety, and post-concussion symptoms than those in the control group, though not on sleep quality.

These symptoms, along with behaviour ratings of executive dysfunction and neuropsychiatric symptom severity, were more prevalent among individuals who had experienced a greater number of self-reported concussions. However, this was unrelated to the number of years played, or position of play. 

Despite frequent subjective memory complaints, the performance of players in cognitive testing did not differ significantly from that of the control group. However, 24 former players, particularly those who had played as forwards and those who had reported more concussions, met the research criteria for CTE syndrome based on neurobehavioural disturbance. This was determined with low provisional levels of certainty: 21 were classed as ‘suggestive’, three as ‘possible’, and none as ‘probable/definite’. Seven of the 24 had cognitive impairment, 12 had neurobehavioral dysregulation, and five had both.

Imaging Findings

3T MRI imaging showed the presence of cavum septum pellucidum in 24% of players, compared with 12% of controls. This was more common in those who had experienced more concussions. They also showed reduced volumes in the frontal and cingulate cortices, with reduced white matter and lower hippocampal volume associated with longer career durations. 

Only 4.6% showed trauma-associated white matter changes on diffusion tensor imaging.

Elevated Blood Biomarkers

Using ultrasensitive digital enzyme-linked immunosorbent assays, researchers analysed fluid biomarkers associated with neurodegeneration. 

Key findings included:

• Phospho-tau217 levels were 17.6% higher in former players
• 23.1% had elevated phospho-tau217
• 9.0% had raised plasma neurofilament light

While levels were lower than in late-onset Alzheimer’s patients, players with elevated markers had more severe neuropsychiatric symptoms, including depression and anxiety.

Frontal brain volumes correlated negatively with neurofilament light, and hippocampal volumes correlated negatively with phospho-tau217.

The findings were published simultaneously in two papers in the journal Brain.

Professor David Sharp, director of the UK Dementia Research Institute Centre for Care Research & Technology at ICL, who co-led the work, said: “We didn’t see any cases of early dementia in this group of former players, which is reassuring. However, the changes in blood biomarkers and brain imaging abnormalities show some long-term effects of repeated head impacts on the brain.”

The studies are set to continue for a further 4 years.

Calls for Action on Player Safety

“Nearly half of dementia cases are linked to known health and lifestyle risk factors, including traumatic brain injury from contact sports like rugby,” said Dr Jacqui Hanley, head of research at Alzheimer’s Research UK. While not much is known about how such injuries cause changes to the brain, “deepening our understanding could ultimately help lower dementia risk for professional sportspeople”.

Hanley called for stronger efforts to reduce head injury in contact sports, stating: “Reducing traumatic brain injury in contact sports is critical to help prevent brain damage and minimise dementia risk for the players.”

The Alzheimer’s Society echoed the concern, noting that professional rugby players face approximately twice the risk of dementia. They called for accurate data on injury patterns and their long-term effects. However, they also stressed that physical activity remains one of the most effective ways to reduce dementia risk.

The Dementia Trust has warned that repeated tackles, scrums, and collisions can contribute to CTE among rugby players, and noted a rise in early-onset dementia among retired professional players. 

In 2023, a group of 260 former professionals launched a lawsuit against World Rugby, the Welsh Rugby Union, and the Rugby Football Union. They alleged negligence in failing to protect players from the risk of neurodegenerative diseases. 

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics. 

The fourth annual virtual conference of the Society for Digital Mental Health (SDMH), June 9-10, 2025, featured presentations and panel discussions on innovative online therapeutics, and on policy affecting their approval, access, and application.

Investigations by students and young researchers were also presented, with these 5 recognized by the organizing committee as best of conference.

Assessing Acceptance in Minorities

While digital therapeutics has the potential to increase access to mental health care, 3 of the featured studies examined how access to, as well as acceptance of, the technology can be problematic for minority groups.

Sigdha Kamarsu, Anxiety Research, Treatment, and Technology (ARTT) Lab, Georgia State University, Atlanta, GA, presented their investigation¹ into whether sexual and gender minority groups encounter additional or different barriers than majority group peers. The investigators applied standardized, self-report measures of attitudes towards psychological online intervention with internet based cognitive behavioral therapy (iCBT) and perceived barriers to psychological treatment. The cohort of 632 participants was grouped into women, men, and gender-queer categories, with sexual orientation categorized as heterosexual, lesbian/gay/bisexual (LGB), and other sexual minority identities (OSMI).

Kamarsu reported that concerns about lack of personal contact when using iCBT were greater for gender-queer individuals compared with men and women, and greater for OSMI compared with heterosexual individuals. OSMI individuals indicated greater confidence in the effectiveness of iCBT than LGB individuals.

“Our results corroborate our hypothesis that sexual and gender minority individuals experience greater negative attitudes, greater attitudinal barriers, and greater practical barriers than their majority group peers,” Kamarsu indicated.

Taylor Myers-Brower, Program for Anxiety, Cognition and Treatment (PACT) Lab, University of Virginia, Charlottesville, described their efforts to culturally tailor MindTrails, a cognitive bias modification program targeting anxious thinking patterns, for Latinx Spanish-speaking individuals.

Eleven treatment-seeking participants provided feedback on a Spanish version of the app over a course of 3 interviews. Factors considered in the interviews varied from technical issues, sources of confusion and the domain of discrimination, to variables affecting engagement and suggestions on personalizing content. The investigators used the feedback to guide iterative changes to the app.

“Early findings suggest positive impressions of a culturally-tailored MindTrails app and highlight potential enhancements to better address the needs of the target audience,” Myers-Brower reported.

Olive Chung-Hui Huang, Department of Psychology, University of Windsor, Ontario, Canada reported on a single arm clinical trial³ conducted with the Center for Addiction and Mental Health (CAMH), Toronto, Ontario that investigated how adoption and acceptability of mindfulness-based apps are affected by social determinants of health such as race, gender, and education.

A mindfulness-based app was provided to a cohort of 183 treatment-seeking adults (65% women, 38.5% sexual minority, 36.1% Black, indigenous, or People of Color [BIPOC], and 35.5% without college education).In the 1-month trial and 3-month follow-up, adoption was indicated by completion of any in-app exercises, acceptability of the app was assessed by questionnaire, engagement was reflected in the number of app exercises completed and the number of minutes in meditation, and attrition was determined from the number of assessments left uncompleted.

Huang reported finding that women, sexual minorities, and below-college educated individuals were more likely to engage with a mindfulness app, and BIPOC persons tended toward less engagement. She anticipates that their future research will “evaluate how mindfulness apps meet the needs of BIPOC or non-binary individuals, and the capacity for apps to be more gender-, trauma-, or culturally-informed.”

Adopting AI and ML

Tyler Schmitt, University of Pittsburgh, reported progress on a project⁴ utilizing a youth research collaborative to validate machine learning (ML) classifiers of social media content. Their goals included identifying social media interactions that expose youth to loneliness and social isolation and developing a mitigating algorithm to improve connectedness and social support.

“Loneliness and perceived isolation are linked to disproportionately higher rates of mental health problems in marginalized youth,” Schmitt related. “These youth may use social media to seek support and connectedness that they cannot find offline.”

The youth collaborative of 14 participants was constituted in partnership with 3 Pittsburgh-based community organizations serving Black, Latinx, and LGBTQ+ youth. The youth held monthly meetings, alternating between in-person and online, that focused on the 4 key concepts of loneliness, social isolation, connectedness, and social support.

“Our youth research partners married research-informed theory and their personal experiences to create working definitions of mental health risk and protective factors that they will use to validate ML classifiers of social media content,” Schmitt explained.

The project is ongoing, with 11 meetings held as of the presentation, of which 9 directly focused on the stated goals. To this point, the project has established consensus on which parts of the working definitions were accurate and identified gaps in the working definitions to be further analyzed in building ML parameters.

Steven Siddals, King’s College London, London, UK, described the experiences of 19 study⁵ participants using generative AI chatbots, like ChatGPT, for mental health issues ranging from symptoms of anxiety and depression to distress over romantic relationships, dealing with loss, and resolving stress and conflict. Siddals et al compared experiences of participants using rule-based chatbots to those using generative AI chatbots and between generative AI chatbots and therapist-guided treatment.

Utilizing semi-structured interviews and reflexive thematic analysis, the investigators derived 4 themes from the reported experiences: emotional sanctuary (validating, nonjudgmental); insightful guidance (valued advice, new perspectives); joy of connection (human-like companionship beyond traditional apps); and “AI Therapist” (augmented therapy, creative new uses). Within these 4 themes, the investigators noted caveats: for emotional sanctuary, appropriate guardrails could be absent; for insightful guidance, there could be insufficient challenge; for joy of connection, it could have been more accessible; and the “AI Therapist” did not lead the process.

In comparing the reported experiences with rule-based vs generative AI chatbots, Siddals related that the former was perceived “more predictable,” “more explainable,” and to have lower risk of bias; while the latter appeared to have “better engagement,” “deeper understanding,” “more flexibility,” and to offer “better quality advice.”

Comparing the experiences with generative AI chatbots to those with clinician-guided treatment, the former was valued by users for around-the-clock availability, lower cost, feeling “less judgmental,” and offering “creative new uses.” In comparison to the bot, the human clinician could lead the process and provide real human connection, and was appreciated for providing “deeper empathy” and “sense of commitment.”

In an earlier published report⁶ on this study, the investigators addressed the safety concern with generative AI chatbots accessed by users in crisis. They relate that several of the study participants experienced meaningful crisis support from generative AI, and they advocate for its use in these circumstances as long as guard rails remain in the algorithm.

While acknowledging that early generative AI chatbots had tragically supported users in dying by suicide, Siddals and colleagues argue against “underestimating the capabilities of generative AI to respond to crisis, and…limiting those capabilities at the times that matter most.”

Dr Bender reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and he provided and managed pharmacy care and drug information services.

References

1. Quirk HD, Anderson PL. Do sexual and gender minority (SGM) groups endorse different barriers and attitudes toward mental health treatment than majority group peers. Presented at annual conference of the Society of Digital Mental Health, June 9-10, 2025.

2. Taylor L, Myers-Brower E, Englander-Fuentes E, et al. User perceptions of a culturally tailored digital cognitive bias modification for interpretation program for anxious Hispanic individuals. Presented at annual conference of the Society of Digital Mental Health, June 9-10, 2025.

3. Huang O, Patel A, Daros A, et al. Social determinants of health are associated with differences in acceptability and engagement with a mindfulness app: Moderation by gender, sexual orientation, race/ethnicity, educational attainment. Presented at annual conference of the Society of Digital Mental Health, June 9-10, 2025.

4. Schmitt TN, Win E, Sreenivasan L, et al. Establishing a youth research collaborative to validate machine learning classifiers of social media content: Leveraging human centered design and youth research partnership. Presented at annual conference of the Society of Digital Mental Health, June 9-10, 2025.

5. Siddals S, Torous J, Coxon A. ChatGPT for mental health? Start by listening to real-life stories. Presented at annual conference of the Society of Digital Mental Health, June 9-10, 2025.

6. Siddals S, Torous J, Coxon A. “It happened to be the perfect thing”: experiences of generative AI chatbots for mental health. Npj Ment Health Res. 2024;3(1):48.

Pollen levels were so extreme in parts of Europe during spring that even people not known to suffer allergies felt the effects of hay fever, data has shown.

The Copernicus Atmosphere Monitoring Service (Cams) observed a seasonal rise in grass and olive pollen release and transport across southern Europe and “extreme levels” of birch pollen in north-eastern regions, it said on Thursday.

Finland, in particular, experienced “extreme daily means of birch pollen” in May “that led to symptoms even among individuals without known allergies”, the EU agency said in its latest air quality update.

Scientists say the climate crisis is altering the production and distribution of pollen and spores, as more and more people report developing allergy symptoms.

As winter frost thaws earlier and spring weather gets warmer, plants and trees flower earlier, extending the pollen season and misery for allergy sufferers.

About a quarter of adults in Europe suffer from airborne allergies, including severe asthma. The proportion among children is 30% to 40%.

That figure is expected to rise to half of Europeans by 2050, according to the World Health Organization.

Laurence Rouil, the director of Cams, said bouts of extremely high pollen levels were not unusual in spring but noted the particular “severity and extent” of this year’s episode.

Air pollution can also increase people’s sensitivity to allergens, while invasive species are spreading into new regions and causing fresh waves of allergies.

Between March and May, air quality across Europe was also affected by wildfires.

April fire emissions in the UK were the second highest since 2003, while the Netherlands recorded unprecedented wildfire emissions levels in this period of the year, Cams said.

Farther afield, large wildfires in eastern Russia sent significant smoke into China and Japan and plumes from major blazes in Canada were observed over Europe in late May, it added.

Jamun (Indian blackberry) and karela (bitter gourd) are two traditional ingredients widely used in Ayurvedic medicine for managing blood sugar levels. When combined as a juice, they form a powerful drink believed to help control diabetes. Both are rich in bioactive compounds that target blood glucose regulation, but can they actually reverse diabetes? How Jamun Helps in Diabetes ControlJamun contains jamboline and jambosine, alkaloids that help regulate the conversion of starch into sugar and improve insulin activity. A 2010 study in the Asian Pacific Journal of Tropical Biomedicine highlighted the anti-diabetic potential of Jamun seeds in lowering blood glucose and oxidative stress in diabetic rats. Its low glycemic index and natural astringent quality further support its traditional use in managing type 2 diabetes. Bitter Gourd’s Blood Sugar BenefitsKarela is a proven natural hypoglycemic agent. It contains compounds like charantin, vicine, and polypeptide-p, which mimic insulin and help lower blood sugar levels. A 2011 study published in the Journal of Ethnopharmacology confirmed karela’s effectiveness in reducing fasting blood glucose in type 2 diabetic patients. The juice of karela is often consumed to support insulin sensitivity and reduce glucose absorption in the intestines.

Can This Juice Reverse Diabetes?While Jamun-Karela juice can significantly help manage blood sugar levels, there is no conclusive evidence that it can reverse diabetes, especially type 2 diabetes. Reversal requires a comprehensive lifestyle change—diet, exercise, weight management, and sometimes medication. This juice can be a valuable addition to such a regimen but not a standalone cure. Studies support improvement in glycemic control, not complete reversal.Clinical Support and CautionsClinical trials are ongoing, but available evidence supports the juice as a complementary therapy. A small 2018 study in Ayurveda Journal of Health showed reduced blood glucose and HbA1c levels after 3 months of daily Jamun-Karela juice intake. However, patients must be cautious. Overconsumption can lead to hypoglycemia, especially when combined with diabetic medications.

Jamun’s slightly sour taste makes it a cooling choice during the rains. It helps digestion, cuts down acidity, and soothes mild bloating. According to a study published in the National Library of Medicine, its antioxidants and bioactive compounds calm the gut and support overall metabolic balance.

How to make this juiceTo make Karela Jamun juice at home, wash and chop 2 medium-sized bitter gourds (karela), removing the seeds, and soak the pieces in salted water for 15 minutes to reduce bitterness. Wash and deseed about 10–12 fresh jamuns or use 2 tablespoons of jamun pulp or powder. Blend the karela and jamun with 1 to 1½ cups of water until smooth, then strain the juice using a fine sieve. Optionally, add a pinch of black salt and a few drops of lemon juice for taste. Drink fresh on an empty stomach in the morning, and store any leftovers in the fridge for up to 24 hours.

The University of Surrey has been awarded £250,000 to combat an aggressive form of childhood cancer.

The grant will fund research into paediatric acute myeloid leukaemia (AML), which the institution said has “tragically low survival rates”.

Researchers will be looking into therapeutic interventions for children diagnosed with the disease as the current treatments “still lead to unacceptable long-term side effects and early mortality,” said Dr Lisie Meira.

The lecturer in DNA damage and ageing at the University of Surrey added: “We need to find safer, more effective alternatives.”

Dr Meira said researchers are working to understand how inhibiting the SET gene can stop the growth of leukemic cells and test new, non-immunosuppressive drugs.

“We’ve already made promising discoveries,” added Dr Maria Teresa Esposito, senior lecturer in biochemistry, who is spearheading the project along with Dr Meira.

Some forms of AML present an “especially grim prognosis”, with only 20 to 50% of infants and children surviving five years after diagnosis, according to the University of Surrey.

Though initial responses to chemo can be positive, relapse rates are “alarmingly high” at 47 to 100%, it added.

The grant is a joint initiative by the CCLG: The Children and Young People’s Cancer Association and the Little Princess Trust.

The U.S. Centers for Disease Control and Prevention (CDC) recently endorsed vaccine recommendations against respiratory syncytial virus (RSV), meningococcal, and chikungunya diseases.

Published on the CDC’s website on June 25, 2025, these recommendations were adopted by the U.S. HHS Secretary.

As the conclusion of last month’s Advisory Committee on Immunization Practices (ACIP) meeting, the members issued the following statement, which is inserted below:

‘Honesty, transparency, and compassion with regard to public health. These are the three pillars that we, the new ACIP members, are guided by. Our central duty is to protect public health, and we understand that we must answer the call for reestablishing confidence in the scientific examination process. This committee strongly supports the use of vaccines and other countermeasures, predicated on evidence-based medicine, including rigorous evaluation and expansive, credible scientific data, for both safety and efficacy.

All stakeholders, including healthcare providers, parents, children, schools, nursing homes, insurance providers, public health agencies, manufacturers, and the rare few who may be harmed by recommended interventions, need to have understandable, digestible, scientifically correct information. This group is committed to providing that information, and in order to do so, we must have data representing large populations. Data collection is a central question that may require constructing a broad risk-benefit analysis. The committee will endeavor to assess the status of programs that are intended to collect data from large populations that have, or have not, received vaccines. These data are needed in order to assess both adverse short- and long-term side effects and to evaluate the magnitude of side effects.

We came to this meeting with no predetermined ideas and will make judgements as if we are treating our own families. Unbiased scientific thinking is fundamental to the committee’s charge. Our votes are recommendations, but we know that some may perceive them as mandates, so we take this responsibility very seriously. We pledge not to hold a vote if there is not sufficient information to enable evaluation of the risks and benefits.

This committee is not in competition with other committees, organizations, or each other – we are all in competition with the infectious diseases, and we will work together to ensure the best outcomes for public health.’

Women who see themselves as having lower social status are more likely than other people to show early signs of heart stress linked to future disease risk, according to a new study led by researchers at McGill and Concordia universities.

One in three women in North America die from heart disease. Yet, women are less likely to receive important cardiac interventions or therapies than men. This highlights the need to rethink how we assess cardiovascular risk in women.”

Dr. Judy Luu, Co-Lead Author, Assistant Professor in McGill’s Department of Medicine and a clinician-scientist at the Research Institute of the McGill University Health Centre

Subjective social status – how people feel they rank compared to others in terms of their social standing – has previously been linked to physical and mental health, with lower social status associated with poorer health. The findings of this study are among the first to show measurable, sex-specific effects in the heart.

More than 400 adults between the ages of 35 and 83, all without diagnosed heart disease, took part in the study. Each completed a questionnaire ranking their social standing on a 10-rung ladder. Cardiac MRI scans then measured early signs of stress in the heart’s tissue.

Women who ranked their social status lower showed more signs of potential inflammation and early scarring in the heart, even when their income and education matched those who ranked their status higher. Men who ranked their social status lower than others with the same income and education did not show these warning signs.

Why might women be more affected?

There are two theories that may explain the findings, said co-lead author Jean-Philippe Gouin, Full Professor of Psychology at Concordia.

“First, subjective social status may better reflect women’s real-life experiences than objective data on their socioeconomic status,” he said. “For example, even with the same education as men, women often earn less or face additional social pressures. So, their self-perception may capture those realities more accurately.”

The second theory is about psychological impact, he said. Women may feel fewer opportunities for upward mobility, which can lead to more stress.

The researchers note that stress is one of the top five risk factors for heart disease in women under 65. Experiences such as trauma, discrimination, and caregiving demands may contribute to the subtle changes in heart tissue observed in this study – suggesting early signs of inflammation, even before disease is diagnosed.

The researchers plan to follow a larger group of participants over time to see whether these early markers predict heart disease.

“We hope our work helps shift the paradigm in cardiac care,” said Luu. “We want to make it normal to discuss mental wellness, social circumstances and stress in routine medical practice.”

A cancer immunotherapy drug that is already on pharmacy shelves is showing fresh potential in the fight against Parkinson’s disease.

In mouse experiments, nivolumab–relatlimab, a fixed‑dose antibody combination used for treating melanoma, blocked the cell‑to‑cell spread of toxic protein clumps that drive the disorder.

More than 8.5 million people worldwide are living with Parkinson’s disease. Current drugs ease symptoms but do little to halt the relentless loss of movement, speech, and independence.

Xiaobo Mao of Johns Hopkins University led an international team that traced the blockade to a newly revealed partnership between two brain proteins, Aplp1 and LAG‑3. Their study offers a practical target for slowing disease progression.

How cancer drug blocks Parkinson’s

Alpha‑synuclein normally helps nerve cells chat across synapses, yet when it misfolds it becomes sticky and forms Lewy bodies.

The group discovered that Aplp1 and LAG‑3 act like twin door handles, swinging the misfolded cargo into neurons together.

“Now that we know how Aplp1 and LAG-3 interact, we have a new way of understanding how alpha‑synuclein contributes to the disease progression of Parkinson’s disease,” confirmed Mao.

Deleting either handle in genetically engineered mice cut protein uptake, but deleting both slashed it by 90 percent.

Using cultured neurons, the team showed that antibodies against LAG‑3 disrupted the partnership and kept most toxic fibrils outside. That hint of druggability set the stage for tests with the approved melanoma therapy.

Repurposing a cancer drug for Parkinson’s

Nivolumab–relatlimab, marketed as Opdualag^TM, won FDA clearance in 2022 as the first combination to target PD‑1 and LAG‑3 checkpoints in tumors.

Because relatlimab binds LAG‑3, the Parkinson’s team wondered whether it could also short‑circuit the neural handshake.

They injected the antibody mix into mice previously dosed with pathogenic fibrils. Treated animals accumulated far fewer Lewy‑like inclusions, keeping the midbrain’s dopamine supply and motor skills intact.

“The anti‑LAG-3 antibody was successful in preventing further spread of alpha‑synuclein seeds in the mouse models,” said Ted Dawson, also from Johns Hopkins.

The effect outperformed complete genetic knockout of LAG‑3 because the drug simultaneously disrupted its partner, Aplp1.

A protein traffic jam in the brain

The brain’s substantia nigra houses dopamine‑producing neurons that fine‑tune movement. When alpha‑synuclein fibrils march from cell to cell, these neurons choke and die, triggering tremor and rigidity.

LAG-3 had been flagged as a fibril receptor before, yet blocking it alone left plenty of pathology. The new work clarifies that Aplp1 forms a complex with LAG-3, which creates a high‑affinity docking site for toxic cargo.

By filming neurons with pH‑sensitive dye, researchers watched fibrils enter healthy cells in minutes. Removal of either handle delayed entry, while removal of both stopped it almost completely.

The discovery may explain why single‑target strategies have struggled to translate. Therapies that ignore Aplp1 risk leaving a back‑door route open for disease spread.

Why Parkinson’s is so difficult

Parkinson’s is diagnosed only after motor symptoms emerge, by which time over half of nigral dopamine neurons have perished. Lewy bodies start forming decades earlier and appear to propagate along neural highways.

Scientists debate whether the fibrils cause disease or merely mark dying cells, yet the correlation is strong enough that reducing their spread remains a key goal.

Animal studies that limit fibril movement often preserve motor behavior and cortical thinking.

The Aplp1–Lag3 duo offers a concise molecular explanation for long‑range propagation. It also supplies a measurable biomarker, their physical interaction, that drug developers can monitor.

Antibodies in action

Preclinical success seldom guarantees human benefit, yet repurposing an approved therapy skips many safety hurdles.

Opdualag’s^TM pharmacokinetics, dosing, and adverse‑event profile are already mapped in thousands of cancer patients.

The antibody crosses the mouse blood–brain barrier at roughly 0.5 percent of plasma levels, similar to other IgG medicines. That level sufficed to curb fibril uptake and protect motor performance in pole and cylinder tests.

If forthcoming primate and human studies confirm brain penetration, clinicians could move swiftly into small Parkinson’s trials using this cancer treatment drug. Outcome measures might track motor scores, cerebrospinal fibril counts, and imaging of nigral dopamine.

Parkinson’s gets help from cancer drug

Cancer checkpoint drugs can unleash immune‑related side effects, including rash, thyroid imbalance, and fatigue. Whether similar events would occur at lower neurological doses remains unknown.

Another question is timing. Most cancer antibodies are delivered in pulses, whereas chronic neuroprotection for Parkinson’s patients might require years of therapy.

Finally, fibril spread is only one facet of Parkinson’s biology. Mitochondrial stress, environmental toxins, and genetics also contribute, so a combination of treatments will likely be needed.

Even so, the ease of testing an off‑the‑shelf cancer medicine for Parkinson’s patients makes this avenue irresistible. As Dawson observed, stopping spread “could significantly slow the progression of Parkinson’s disease.”

The study is published in Nature Communications.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–