Author: anna_acnr

New immune map of thymus reveals potential clues to myasthenia gravis

Posted on August 19, 2026 by - Myasthenia Gravis

Researchers have identified a previously unrecognised immune environment in the thymus that may help explain why myasthenia gravis (MG) persists in some patients despite treatment. The findings provide new insights into the biology of the autoimmune disease and could point towards future therapeutic targets.

Published in Science Advances, the Northwestern Medicine study combined single-cell RNA sequencing, immune receptor analysis and spatial transcriptomics to investigate thymus tissue from people with MG. The researchers analysed 23 samples from 16 patients and integrated their findings with existing datasets to create an atlas containing almost 347,000 cells.

Myasthenia gravis occurs when the immune system disrupts communication between nerves and muscles, causing fluctuating weakness and fatigue. Symptoms commonly affect the muscles controlling the eyes, face, speech, swallowing and chewing, while severe disease can affect breathing.

Rather than finding one dominant population of abnormal B cells, the researchers identified a diverse population of class-switched B cells clustered around abnormal germinal centres in MG thymus tissue. These cells appeared to depend on survival signals involving B-cell activating factor (BAFF) and B-cell maturation antigen (BCMA).

The findings suggest that the tissue environment itself may help sustain potentially harmful B cells. The researchers describe this as a possible shift away from normal immune-control mechanisms towards an alternative survival pathway.

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The discovery could help explain why antibody levels do not always correspond closely with disease severity and why some patients continue to experience symptoms following thymectomy. However, the study did not directly establish that the identified pathways cause persistent disease.

The researchers emphasised that the findings do not change current treatment recommendations. Thymectomy remains an evidence-based option for appropriately selected patients, while further studies are needed to determine whether the BAFF and BCMA pathways can be safely targeted.

Future research will investigate whether these pathways actively contribute to MG progression and whether targeting them could help restore immune tolerance.

This news item has been summarised using AI and checked by humans before publication.

Sources

newswise.com

science.org

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One silent MRI lesion may be enough to consider stronger MS treatment

Posted on August 17, 2026 by - Multiple Sclerosis

A large international study suggests that even a single clinically silent MRI lesion may identify people with relapsing-remitting multiple sclerosis (RRMS) who are at increased risk of future relapses and disability worsening. The findings, published in Brain, challenge current approaches that generally reserve treatment escalation for patients who develop multiple new lesions.

Clinically silent lesions are areas of new or enlarging damage seen on MRI without an accompanying relapse or measurable worsening of disability. Although such lesions can indicate ongoing disease activity, a single lesion has sometimes been regarded as minimal radiological activity that does not necessarily warrant a change in treatment.

Researchers analysed data from more than 10,000 adults with RRMS enrolled in the MSBase registry. Participants had been clinically stable on disease-modifying therapy (DMT) and underwent routine MRI monitoring across centres in 26 countries between 2007 and 2025.

At the first eligible MRI assessment, 81.1% of participants had no silent lesions, 9.2% had one lesion and 9.7% had multiple lesions.

Over approximately two years, patients with a single silent lesion had a 59% higher adjusted risk of relapse compared with those without lesions. Those with multiple lesions had a 94% higher risk. The risk of confirmed disability worsening was also higher, by 35% for a single lesion and 42% for multiple lesions.

The researchers also used registry data to emulate a clinical trial examining treatment escalation. Among 2,264 patients receiving platform or moderate-efficacy DMTs, escalation within six months of detecting silent MRI activity was associated with more than a halving of the estimated four-year relapse risk.

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However, escalation did not significantly reduce confirmed disability worsening. The authors suggested that longer follow-up may be needed to detect an effect, while noting that current DMTs have greater effects on inflammatory disease activity than on some mechanisms driving progressive disability.

The findings suggest that even one clinically silent lesion could be an important indicator of breakthrough disease activity. The researchers argue that treatment escalation should be considered after a single lesion, alongside careful assessment of the risks and benefits of higher-efficacy therapies.

This news item has been summarised using AI and checked by humans before publication.

Sources

academic.oup.com

multiplesclerosisnewstoday.com

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Gut bacteria may reach the brain through the vagus nerve, mouse study suggests

Posted on August 10, 2026 by - Alzheimer's Disease, Neurodegenerative diseases, Parkinson’s Disease

Researchers have identified a potential new pathway by which gut bacteria may enter the brain, providing fresh insight into the gut-brain axis and its possible role in neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease.

The study, published in PLOS Biology, found that a short-term high-fat diet disrupted the intestinal barrier in mice, allowing live bacteria to migrate from the gut to the brain via the vagus nerve. The findings add to growing evidence that gut health may influence neurological disease, although the research was conducted entirely in animals and has not yet been shown to occur in humans.

Scientists at Emory University fed mice a high-fat diet for several days, which rapidly altered the gut microbiome and increased intestinal permeability, commonly referred to as a “leaky gut”. Using bacterial cultures and genetically barcoded bacteria, the researchers tracked the movement of microbes from the intestine into the vagus nerve before they appeared in the brain.

Importantly, bacteria were not detected in the bloodstream or other organs, suggesting they travelled directly along the vagus nerve rather than spreading through the circulation. When researchers surgically severed one branch of the vagus nerve, bacterial migration to the brain was significantly reduced, strengthening evidence that this nerve serves as the primary route.

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The team also observed impaired gut barrier function in mouse models of both Parkinson’s disease and Alzheimer’s disease. Encouragingly, when mice returned to a standard diet for two weeks, gut barrier integrity improved and bacterial levels in the brain declined.

The researchers caution that the work does not demonstrate that bacteria cause neurodegenerative diseases. Instead, it raises the possibility that bacterial migration may contribute to inflammation or disease progression in susceptible individuals.

Further studies are needed to determine whether the same mechanism occurs in people and whether improving gut barrier function through diet or other interventions could reduce the risk of neurological disease. The findings also support continued investigation of the gut-brain axis as a potential target for future therapies and early diagnostic biomarkers.

This news item has been summarised using AI and checked by humans before publication.

Sources

PLOS Biology

Medscape

Emory University

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Personalised gene therapy shows promise for rare genetic epilepsy

Posted on August 7, 2026 by - Epilepsy

Two children with a rare and severe genetic form of epilepsy experienced substantial reductions in seizures and developmental improvements after receiving personalised gene therapy designed specifically for their individual genetic mutations, according to a study published in Nature Medicine.

Researchers from the University of California San Diego and the Rady Children’s Institute for Genomic Medicine treated two patients with SCN2A-related developmental epileptic encephalopathy (DEE), a rare disorder caused by mutations in the SCN2A gene that can lead to severe epilepsy, developmental delay, autism and movement disorders. Conventional anti-seizure medications often provide limited benefit because they do not address the underlying genetic cause.

The team developed customised antisense oligonucleotides (ASOs), short synthetic DNA molecules designed to selectively silence the disease-causing copy of the SCN2A gene while preserving the normal copy. The therapy was administered into the spinal fluid every two to three months over a two-year period, with each patient acting as their own control.

The younger patient, aged nine at the start of treatment, experienced a 26% reduction in seizure frequency. The older patient, who was 14 years old when treatment began, achieved a 90% reduction in seizures and experienced prolonged seizure-free periods.

Both children were able to reduce their anti-seizure medication burden and showed improvements in language, motor function, sensory processing and adaptive behaviour. The older patient achieved independent walking for the first time at the age of 15, while chronic gastrointestinal symptoms also improved.

No serious treatment-related adverse events were reported, and routine laboratory investigations, electrocardiograms and electroencephalograms remained stable throughout the study. Researchers also found that adjusting the dosing interval helped maintain the older patient’s newly acquired ability to walk independently.

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Although the treatment remains experimental, the authors believe the study demonstrates the feasibility of developing highly personalised genetic therapies for patients with ultra-rare neurological disorders. They suggest the approach could provide a framework for rapidly translating individual genetic diagnoses into tailored treatments for other single-gene diseases.

The authors caution that larger studies will be required to establish the long-term safety, effectiveness and wider applicability of this precision medicine approach.

This news item has been summarised using AI and checked by humans before publication.

Sources

Nature Medicine

University of California San Diego

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Eye movement biomarker may improve measurement of Parkinson’s disease progression

Posted on August 5, 2026 by - Parkinson’s Disease

A novel eye movement biomarker has shown greater sensitivity than the current clinical gold standard for measuring Parkinson’s disease progression, according to a multicentre study that could help improve the evaluation of disease-modifying therapies in clinical trials.

Published in Pharmaceutical Medicine, the study found that NeuraLight’s digital biomarker, based on eye movement analysis, detected measurable disease progression in people with Parkinson’s disease over time, while the widely used Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) did not identify comparable changes.

The international study followed 280 people with Parkinson’s disease enrolled in two prospective clinical studies conducted across five countries. Researchers assessed disease progression longitudinally using both conventional clinical rating scales and objective eye movement measurements.

The biomarker, known as amplitude of saccadic hypometria (ASH), measures how accurately the eyes move towards visual targets, providing an objective assessment of basal ganglia function, the brain circuitry primarily affected in Parkinson’s disease. Across both patient cohorts, ASH demonstrated a highly reproducible decline over time, with statistically significant changes observed consistently across study sites.

In contrast, clinician-rated MDS-UPDRS Part III motor scores did not demonstrate statistically significant progression over the same period. The authors suggest this may reflect the inherent variability associated with clinician-based assessments, which can differ between raters and clinical centres and make subtle disease progression more difficult to detect.

The study was led by Professors Olivier Rascol and Christopher G. Goetz, both of whom were involved in developing the MDS-UPDRS, together with an international group of movement disorders specialists.

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The researchers believe objective digital biomarkers could improve the sensitivity of clinical trials evaluating therapies designed to slow disease progression. More accurate measurement of progression may reduce the risk of potentially effective treatments being overlooked because existing assessment tools fail to detect meaningful clinical change.

While the findings are encouraging, further prospective studies will be needed to confirm the biomarker’s performance in larger patient populations and determine whether it can be adopted as a validated outcome measure in future Parkinson’s disease clinical trials.

This news item has been summarised using AI and checked by humans before publication.

Sources

Pharmaceutical Medicine

ClinicalTrials.gov: NCT05795023

ClinicalTrials.gov: NCT05862649

NeuraLight

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Study suggests protein clumps may help protect brain cells in Huntington’s disease

Posted on August 3, 2026 by - Huntington's disease

Protein clumps that accumulate in the brains of people with Huntington’s disease and other neurodegenerative disorders may play a protective rather than harmful role, according to new research that challenges a long-standing theory of disease progression.

Published in Cell Death & Differentiation, the study found that so-called inclusion bodies, long regarded as toxic deposits that contribute to neuronal death, may instead act as a defence mechanism by isolating harmful misfolded proteins and helping nerve cells survive periods of stress.

Researchers at the Hebrew University of Jerusalem used induced pluripotent stem cells derived from patients with Huntington’s disease to generate genetically identical human neurons. Some of these cells naturally formed inclusion bodies while others did not, allowing the team to directly compare their responses to cellular stress.

When exposed to stress-inducing conditions, neurons lacking inclusion bodies were significantly more likely to die than those containing the protein aggregates. The findings suggest that inclusion bodies function as a biological “quarantine” system, sequestering toxic proteins and limiting damage to the rest of the cell.

The study also identified activating transcription factor 3 (ATF3) as a key regulator of this protective response. Removing ATF3 prevented neurons from forming inclusion bodies and made them substantially more vulnerable to stress. Further analysis showed that ATF3 activates genes involved in the unfolded protein response, an important cellular pathway that helps repair damage caused by misfolded proteins.

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The researchers also observed increased production of inflammatory signalling molecules, including interleukin-8 (IL-8), in neurons containing inclusion bodies. Similar molecular changes were identified in brain tissue from people with Huntington’s disease, suggesting the findings may be relevant to disease processes in patients.

The authors propose that future therapies could focus on enhancing the brain’s natural protective mechanisms rather than attempting to eliminate protein aggregates. However, they emphasise that further research is needed to determine whether boosting ATF3 activity or promoting inclusion body formation would be safe and beneficial in patients with Huntington’s disease or other neurodegenerative disorders.

The findings add to growing evidence that some pathological features of neurodegenerative diseases may represent protective cellular responses rather than the primary cause of neuronal damage.

This article has been summarised using AI and checked by humans before publication.

Sources

Cell Death & Differentiation

Hebrew University of Jerusalem

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Study maps brain protein linked to epilepsy and identifies potential drug target

Posted on July 31, 2026 by - Epilepsy

Researchers have determined the first high-resolution structure of a brain protein linked to epilepsy, autism spectrum disorder and other neurological conditions, while also developing the first compounds capable of blocking its activity, offering a potential new avenue for neurological drug discovery.

Published in Nature Communications, the study focused on the neuronal protein NBCn2, a transporter that helps regulate acid-base balance within brain cells by moving sodium and carbonate ions across cell membranes. Although genetic variants affecting NBCn2 have previously been associated with epilepsy and autism, little has been known about its structure or function, limiting efforts to develop targeted therapies.

Scientists at the Icahn School of Medicine at Mount Sinai used cryo-electron microscopy to produce the first detailed structural images of NBCn2, revealing how the transporter binds and moves ions that help regulate neuronal excitability.

Using this structural information, the team designed and screened compounds capable of inhibiting NBCn2. Laboratory experiments in cultured neurons and mouse brain tissue showed that one of these compounds reduced electrical signalling between nerve cells, demonstrating that the transporter can be pharmacologically targeted.

The researchers also identified an unexpected mechanism by which NBCn2 binds sodium and carbonate ions. The binding arrangement differed from that seen in related transport proteins, suggesting opportunities to design drugs that selectively target NBCn2 while avoiding similar transporters.

The study combined cryo-electron microscopy with artificial intelligence-based structural prediction, computer modelling and virtual screening of millions of chemical compounds to identify potential inhibitors before testing them experimentally.

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The authors stress that the compounds are early-stage research tools rather than candidate medicines. Further work will be needed to improve their potency and selectivity and to evaluate their safety and effectiveness in animal models and human-derived systems before clinical development can be considered.

Nevertheless, the findings provide an important framework for investigating NBCn2 as a therapeutic target for epilepsy and other neurological disorders characterised by excessive neuronal activity. The researchers also believe the approach could accelerate the study of other previously understudied transporter proteins involved in diseases of the nervous system.

This news item has been summarised using AI and checked by humans before publication.

Sources

Nature Communications: Structural insights enable drug discovery for the neuronal NBCn2 carbonate transporter

Mount Sinai Health System

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Researchers identify potential new therapeutic targets for progressive multiple sclerosis

Posted on July 29, 2026 by - Multiple Sclerosis

Researchers have identified six proteins that could become future therapeutic targets for slowing progression in multiple sclerosis (MS), raising the possibility of developing new treatments or repurposing existing medicines for progressive disease.

Published in the Journal of Neuroinflammation, the study combined large-scale genetic and protein data to identify biological pathways linked to disability progression in MS. The findings provide new insights into the mechanisms underlying progressive disease, an area where effective treatment options remain limited.

Current disease-modifying therapies are highly effective at reducing relapses by suppressing inflammation but have less impact on the neurodegenerative processes that drive disability accumulation in progressive MS. The researchers therefore used a multi-omics approach, integrating genome-wide association study data with protein quantitative trait loci analyses, to identify proteins most strongly associated with disease progression.

After analysing multiple datasets and assessing biological relevance, cell-specific expression and potential drug interactions, the team prioritised six proteins as promising therapeutic targets: RRM2B, CBR1, ETFA, DNM3, CAB39L and NMRAL1.

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Among these, RRM2B attracted particular interest because it showed potential interactions with cladribine, marketed as Mavenclad, an approved treatment for relapsing forms of MS. The findings suggest that cladribine may influence pathways involved in neurodegeneration as well as inflammation, supporting further investigation of its role in slowing disease progression. The researchers also identified the cancer medicine clofarabine as another potential candidate for future evaluation.

The remaining proteins are involved in processes including oxidative stress, energy metabolism, neuronal signalling and immune regulation, all of which have been implicated in MS progression. The analysis also highlighted several compounds, including naturally occurring flavonoids, that may warrant investigation as potential adjunctive therapies.

The authors stress that these findings are based on genetic and computational analyses and do not demonstrate that targeting these proteins will slow MS progression. Further laboratory studies and carefully designed clinical trials will be required to validate the biological importance of these targets and determine whether they can be translated into effective treatments.

This news item has been summarised using AI and checked by humans before publication.

Sources

Multiple Sclerosis News Today

Journal of Neuroinflammation

Karolinska Institutet

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Decline in work productivity may begin years before early-onset dementia diagnosis

Posted on July 27, 2026 by - Alzheimer's Disease, Dementia

People who develop early-onset dementia may experience a gradual decline in work productivity up to 15 years before receiving a diagnosis, according to a new Finnish study published in Neurology. The findings highlight the substantial personal and economic impact of dementia during working age and suggest that subtle cognitive changes may affect employment long before the condition is recognised.

Researchers analysed data from 793 people diagnosed with early-onset dementia before the age of 65 and compared them with 7,926 age- and sex-matched individuals without dementia. Using national health, education and tax registries, the team examined annual income as a measure of work productivity while accounting for factors such as education level and other medical conditions.

Across the study period, people with early-onset dementia experienced average productivity losses of €74,577 per person compared with those without dementia, equivalent to around €12,000 annually.

The timing of productivity decline varied according to the underlying type of dementia. For people with Alzheimer’s disease, reduced productivity became apparent around six years before diagnosis. Those with frontotemporal dementia showed declining productivity up to 11 years before diagnosis, while individuals with alpha-synucleinopathies, including dementia with Lewy bodies and Parkinson’s disease dementia, demonstrated losses only at the time of diagnosis. Productivity losses in other dementia types remained consistently high throughout the observation period.

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Lead author Dr Eino Solje of the University of Eastern Finland said the findings reflect the considerable socioeconomic burden associated with early-onset dementia and may partly result from delays in diagnosis that allow symptoms to go unrecognised for many years.

The researchers emphasise that the study demonstrates an association rather than proving that early-onset dementia directly causes reduced work productivity. They suggest future research should incorporate longitudinal neuropsychological assessments to better understand cognitive decline over time and investigate interventions that could delay productivity losses and support people to remain in employment for longer.

The authors believe earlier recognition of cognitive symptoms in working-age adults could improve both clinical care and long-term socioeconomic outcomes.

This news item has been summarised using AI and checked by humans before publication.

Sources

American Academy of Neurology

Neurology

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Explainable AI predicts cognitive decline in multiple sclerosis with 90% accuracy

Posted on July 24, 2026 by - Multiple Sclerosis

Researchers have developed an explainable artificial intelligence (AI) model capable of predicting future cognitive decline in people with multiple sclerosis (MS) with around 90% accuracy, offering a potential new tool to support earlier intervention and more personalised patient care.

Published in the European Journal of Neurology, the study combined MRI brain scans with clinical and demographic data from 224 people with MS and 115 healthy controls. Participants underwent detailed neurological, cognitive and MRI assessments and were followed for a median of 3.4 years.

The researchers used the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria to classify patients with Mild or Major Neurocognitive Disorder (NCD), a framework that considers both cognitive performance and its impact on everyday functioning.

At the start of the study, 4% of participants met the criteria for Mild NCD and 11% for Major NCD. During follow-up, 12% experienced cognitive deterioration, with some progressing from normal cognition to Mild or Major NCD.

The team developed a hybrid deep learning model that analysed structural MRI scans alongside information including age, disability level, disease duration, cognitive reserve and brain volumetric measurements. The model achieved a validation accuracy of 90% and an area under the curve of 0.89, indicating strong predictive performance.

Unlike many previous AI systems, the model was designed to explain how it reached its predictions. The most influential factors associated with future cognitive decline were cortical grey matter volume, age, thalamic volume, hippocampal volume, T2 lesion volume and cognitive reserve.

Analysis of MRI data also highlighted the importance of frontal brain regions, together with temporal, parietal, occipital and cerebellar structures that are known to support memory, attention, processing speed and executive function.

The authors say explainable AI could help neurologists identify patients at greatest risk of cognitive deterioration before symptoms become more severe, allowing closer monitoring, earlier cognitive rehabilitation and potentially more personalised treatment strategies.

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Although the findings are promising, the researchers note that the model requires validation in larger, independent patient populations before it can be adopted in routine clinical practice.

This news item has been summarised using AI and checked by humans before publication.

Sources

European Journal of Neurology: Explainable Artificial Intelligence to Predict Neurocognitive Disorder Progression in Multiple Sclerosis Using MRI and Clinical Data

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