While recent therapies have the potential to stall or delay the progression of multiple sclerosis, a new study shows that young Black and Hispanic women fare worse than young white women.
Minority women were more likely to have more advanced disease and faced greater challenges in pregnancy, the researchers reported in their study, published in the journal Neurology on Jan. 23, 2024.
Researchers tracked medical records at nine MS centres nationwide for 294 women whose pregnancies resulted in live births. Approximately half of the patients were white, just over one-quarter were Black, and the remainder were Hispanic.
The researchers found that close to 95% of the participants had relapsing-onset MS, the most common type of the disease in which flare-ups alternate with periods of recovery. In MS, which predominantly affects women, the immune system attacks myelin, the protective covering of nerve fibres, disrupting nerve impulses. MS symptoms include bowel and bladder problems, pain, and difficulties with vision and walking.
“We found that Black and Hispanic women faced socioeconomic disadvantages that were likely to hurt their health,” said senior author Riley Bove, M.D., of the UCSF Department of Neurology and the Weill Institute for Neurosciences. “At the time of conception, they were more likely to live in under-resourced neighbourhoods, to be unemployed and less likely to have private health insurance.”
Black and Hispanic women were ages 31 and 30, respectively, at the time of conception – younger than the white women, who were 34. The minority women had an Expanded Disability Status Scale (EDSS) ranking of 1.5, corresponding to symptoms in more than one functional system. White women had an average EDSS ranking of 1, the equivalent of symptoms in one functional system such as vision, bowel and bladder, or balance and coordination.
Higher inflammation levels may signal MS progression
Minority women also had higher levels of inflammation both before and after pregnancy, an indication that they were more susceptible to myelin loss, and injury to the underlying axon, part of the nerve cell, representing disease progression. However, no significant racial differences were identified in MS care, including the type of treatment prescribed and how the disease was managed before and after pregnancy, said Bove.
“Drug companies’ financial assistance programs for low-income patients may enable them to access more effective therapies,” said Bove. But there was no data on other factors that may influence outcome, “such as racism among clinicians, severity of accompanying medical conditions and access to experts, like lactation consultants,” she said.
The researchers found that minority women were slightly less likely to receive a 14-week ultrasound, Black women were more than twice as likely to undergo emergency C-sections as Hispanic women, and minority women were more likely to give birth to lower-birthweight babies. All three groups had similar rates of breastfeeding, which is protective against MS relapse, but white mothers breastfed for six months, versus 4.5 months for the minority mothers.
“What we are seeing is that underrepresented women with MS start their pregnancies with higher disability and fewer health care resources,” said Bove. “Our findings highlight the importance of considering race-ethnicity and disability in women with MS. They also suggest that socioeconomic opportunity, rather than MS-related care, may lay the foundation for disparities in MS outcomes.”
The new study has found the genes that significantly increase a person’s risk of developing multiple sclerosis (MS) were introduced into north-western Europe around 5,000 years ago by sheep and cattle herders migrating from the east. CREDIT SayoStudio
Researchers have created the world’s largest ancient human gene bank by analysing the bones and teeth of almost 5,000 humans who lived across Western Europe and Asia up to 34,000 years ago.
By sequencing ancient human DNA and comparing it to modern-day samples, the international team of experts mapped the historical spread of genes – and diseases – over time as populations migrated.
The ‘astounding’ results have been revealed in four trailblazing research papers published today (10 January 2024) in the same issue of Nature and provide a new biological understanding of debilitating disorders.
The extraordinary study involved a large international team led by Professor Eske Willerslev at the Universities of Cambridge and Copenhagen, Professor Thomas Werge at the University of Copenhagen, and Professor Rasmus Nielsen at University of California, Berkeley and involved contributions from 175 researchers from around the globe.
The scientists found:
The startling origins of neurodegenerative diseases including multiple sclerosis
Why northern Europeans today are taller than people from southern Europe
How major migration around 5,000 years ago introduced risk genes into the population in north-western Europe – leaving a legacy of higher rates of MS today
Carrying the MS gene was an advantage at the time as it protected ancient farmers from catching infectious diseases from their sheep and cattle
Genes known to increase the risk of diseases such as Alzheimer’s and type 2 diabetes were traced back to hunter gatherers
Future analysis is hoped to reveal more about the genetic markers of autism, ADHD, schizophrenia, bipolar disorder, and depression
Northern Europe has the highest prevalence of multiple sclerosis in the world. A new study has found the genes that significantly increase a person’s risk of developing multiple sclerosis (MS) were introduced into north-western Europe around 5,000 years ago by sheep and cattle herders migrating from the east.
By analysing the DNA of ancient human bones and teeth, found at documented locations across Eurasia, researchers traced the geographical spread of MS from its origins on the Pontic Steppe (a region spanning parts of what are now Ukraine, South-West Russia and the West Kazakhstan Region).
They found that the genetic variants associated with a risk of developing MS ‘travelled’ with the Yamnaya people – livestock herders who migrated over the Pontic Steppe into North-Western Europe.
These genetic variants provided a survival advantage to the Yamnaya people, most likely by protecting them from catching infections from their sheep and cattle. But they also increased the risk of developing MS.
“It must have been a distinct advantage for the Yamnaya people to carry the MS risk genes, even after arriving in Europe, despite the fact that these genes undeniably increased their risk of developing MS,” said Professor Eske Willerslev, jointly at the Universities of Cambridge and Copenhagen and a Fellow of St John’s College, an expert in analysis of ancient DNA and Director of the project.
He added: “These results change our view of the causes of multiple sclerosis and have implications for the way it is treated.”
The age of specimens ranges from the Mesolithic and Neolithic through the Bronze Age, Iron Age and Viking period into the Middle Ages. The oldest genome in the data set is from an individual who lived approximately 34,000 years ago.
The findings provide an explanation for the ‘North-South Gradient’, in which there are around twice as many modern-day cases of MS in northern Europe than southern Europe, which has long been a mystery to researchers.
From a genetic perspective, the Yamnaya people are thought to be the ancestors of the present-day inhabitants of much of North-Western Europe. Their genetic influence on today’s population of southern Europe is much weaker.
Previous studies have identified 233 genetic variants that increase the risk of developing MS. These variants, also affected by environmental and lifestyle factors, increase disease risk by around 30 percent. The new research found that this modern-day genetic risk profile for MS is also present in bones and teeth that are thousands of years old.
“These results astounded us all. They provide a huge leap forward in our understanding of the evolution of MS and other autoimmune diseases. Showing how the lifestyles of our ancestors impacted modern disease risk just highlights how much we are the recipients of ancient immune systems in a modern world,” said Dr William Barrie, a postdoc in the University of Cambridge’s Department of Zoology and co-author of the paper.
Multiple sclerosis is a neurodegenerative disease in which the body’s immune system mistakenly attacks the ‘insulation’ surrounding the nerve fibres of the brain and spinal cord. This causes symptom flares known as relapses as well as longer-term degeneration, known as progression.
Professor Lars Fugger, a co-author of the MS study professor and consultant physician at John Radcliffe Hospital, University of Oxford, said: “This means we can now understand and seek to treat MS for what it actually is: the result of a genetic adaptation to certain environmental conditions that occurred back in our prehistory.”
Professor Astrid Iversen, another co-author based at the University of Oxford, said: “We now lead very different lives to those of our ancestors in terms of hygiene, diet, and medical treatment options and this combined with our evolutionary history means we may be more susceptible to certain diseases than our ancestors were, including autoimmune diseases such as MS.”
The new findings were made possible by the analysis of data held in a unique gene bank of ancient DNA, created by the researchers over the past five years with funding from the Lundbeck Foundation.
This is the first gene bank of its kind in the world and already it has enabled fascinating new insights in areas from ancient human migrations, to genetically-determined risk profiles for the development of brain disorders.
By analysing the bones and teeth of almost 5,000 ancient humans, held in museum collections across Europe and Western Asia, the researchers generated DNA profiles ranging across the Mesolithic and Neolithic through the Bronze Age, Iron Age and Viking period into the Middle Ages. They compared the ancient DNA data to modern DNA from 400,000 people living in Britain, held in the UK Biobank.
“Creating a gene bank of ancient DNA from Eurasia’s past human inhabitants was a colossal project, involving collaboration with museums across the region,” said Willerslev.
He added: “We’ve demonstrated that our gene bank works as a precision tool that can give us new insights into human diseases, when combined with analyses of present-day human DNA data and inputs from several other research fields. That in itself is amazing, and there’s no doubt it has many applications beyond MS research.”
The team now plans to investigate other neurological conditions including Parkinson’s and Alzheimer’s diseases, and psychiatric disorders including ADHD and schizophrenia.
They have received requests from disease researchers across the world for access to the ancient DNA profiles, and eventually aim to make the gene bank open access.
The research was funded by a €8M grant from the Lundbeck Foundation, and conducted at the Lundbeck Foundation Geogenetics Centre at the University of Copenhagen.
Jan Egebjerg, Director of Research at the Lundbeck Foundation, said: “The rationale for awarding such a large research grant to this project, as the Lundbeck Foundation did back in 2018, was that if it all worked out, it would represent a trail-blazing means of gaining a deeper understanding of how the genetic architecture underlying brain disorders evolved over time. And brain disorders are our specific focus area.”
A combination of only 11 proteins can predict long-term disability outcomes in multiple sclerosis (MS) for different individuals. The identified proteins could be used to tailor treatments to the individual based on the expected severity of the disease. The study, led by researchers at Linköping University in Sweden, has been published in the journal Nature Communications.
“A combination of 11 proteins predicted both short and long-term disease activity and disability outcomes. We also concluded that it’s important to measure these proteins in cerebrospinal fluid, which better reflects what’s going on in the central nervous system, compared with measuring in the blood,” says Julia Åkesson, doctoral student at Linköping University and the University of Skövde.
In multiple sclerosis, the immune system attacks the person’s own body, damaging nerves in the brain and in the spinal cord. What is attacked primarily is a fatty compound called myelin, which surrounds and insulates the nerve axons so that signals can be transmitted. When myelin is damaged, transmission becomes less efficient.
Disease progression in multiple sclerosis varies considerably from person to person. To those for whom a more severe disease is predicted, it is important not to lose valuable time at the onset of the disease but to get the right treatment quickly. The researchers behind the current study, which is a collaboration between Linköping University, the Karolinska Institute and the University of Skövde, wanted to find out whether it was possible to detect at an early stage of disease which patients would require a more powerful treatment. Being able to do so would be relevant both to physicians and those living with MS.
“I think we’ve come one step closer to an analysis tool for selecting which patients would need more effective treatment in an early stage of the disease. But such a treatment may have side effects and be relatively expensive, and some patients don’t need it,” says Mika Gustafsson, professor of bioinformatics at the Department of Physics, Chemistry and Biology at Linköping University, who led the study.
Finding markers linked to disease severity many years ahead is a complicated challenge. In their study, the researchers analysed nearly 1,500 proteins in samples from 92 people with suspected or recently diagnosed MS. Data from the protein analyses were combined with a large amount of information from the patients’ journals, such as disability, results from MRI scans of the nervous system, and treatments received. Using machine learning, the researchers found a number of proteins that could predict disease progression.
“Having a panel consisting of only 11 proteins makes it easy should anyone want to develop analysis for this. It won’t be as costly as measuring 1,500 proteins, so we’ve really narrowed it down to make it useful for others wanting to take this further,” says Sara Hojjati, doctoral student at the Department of Biomedical and Clinical Sciences at Linköping University.
The research team also found that a specific protein, leaking from damaged nerve axons, is a reliable biomarker for disease activity in the short term. This protein is called neurofilament light chain, NfL. These findings confirm earlier research on the use of NfL to identify nerve damage and also suggest that the protein indicates how active the disease is.
One of the main strengths of the study is that the combination of proteins found in the patient group from which samples were taken at Linköping University Hospital was later confirmed in a separate group consisting of 51 MS patients sampled at the Karolinska University Hospital in Stockholm.
This study is the first to measure such a large amount of proteins with a highly sensitive method, proximity extension assay, combined with next-generation sequencing, PEA-NGS. This technology allows for high-accuracy measuring also of very small amounts, which is important as these proteins are often present in very low levels.
Researchers identified immune cells as a potential key factor for protection against MS disease
The underlying cause of MS has not yet been fully clarified, but a connection with the Epstein-Barr virus (EBV) has long been suspected. In most patients who develop MS, specific immune responses against EBV are detectable, which are also directed against certain structures of the central nervous system and thus contribute to the development of MS. Until now. However, it was unclear why an EBV infection, one of the most common and lifelong persistent viral infections in humans, only leads to MS in a small number of people. A research group at the Centre for Virology led by Elisabeth Puchhammer-Stöckl, in cooperation with a team from the Department of Neurology at the Medical University of Vienna led by Thomas Berger and Paulus Rommer, has now shown that the risk of MS is particularly high in people with a combination of certain host factors and virus variants.
Natural killer cells as a potential protective factor To be specific, the investigations revealed a greatly increased risk of MS, if, on the one hand, the EBV-specific and autoreactive immune responses are strong and, on the other hand, the patients are unable to control this autoimmunity efficiently. The study authors identified a subgroup of the natural killer cells of the human immune system as a potential key factor for protection against MS. “These immune responses could therefore play a decisive role in the development of future vaccines,” says Hannes Vietzen from the Centre for Virology, first author of the study, describing the new possibilities that arise from the research work with regard to the prevention and early detection of MS. According to the investigations, the development of MS proved to be dependent on certain genetic factors as well as on infection with a specific EBV virus variant, which, according to the laboratory experiments, leads to a significantly weakened immune response against the autoreactive processes and thus contributes to the development of MS. “It may be helpful to analyse the EBV variants detected in these patients in order to identify patients at risk at an early stage,” says Hannes Vietzen in the run-up to further studies that are intended to deepen these findings.
Uncovering the neural correlates of cognitive fatigue: a comparative analysis across multiple sclerosis, traumatic brain injury, and control populations
– In an innovative study, researchers have conducted the first systematic investigation of the effects of cognitive fatigue by using two different tasks across three distinct populations: multiple sclerosis, traumatic brain injury, and controls. T
This study compared a group with multiple sclerosis and a group with traumatic brain injury to a control group to assess the relationships among cognitive fatigue, behavioural performance, and brain activation.
Two distinct tasks – a working memory task and a processing speed task – were used to induce cognitive fatigue while functional neuroimaging data were collected. Findings revealed that while the two clinical groups reported more cognitive fatigue than the control group, the accrual of cognitive fatigue was consistent across all participants, and cognitive fatigue ratings remained stable across tasks. This suggests that the experience of cognitive fatigue is not task-specific but rather a consistent state triggered by cognitive exertion.
Moreover, the study uncovered that increased cognitive fatigue correlated with longer task response times across all groups. Neuroimaging data showed that activation in the caudate nucleus and thalamus was consistently related to cognitive fatigue levels across all three groups, underscoring these brain regions as central to the experience of cognitive fatigue. Interestingly, variations in activation patterns were observed more dorsally in the caudate nucleus, indicating that this region’s sensitivity may be linked to the type of brain damage sustained.
“The similarities and differences of our findings across populations, regardless of the task used to induce fatigue, provide new insights into cognitive fatigue resulting from brain injury and disease,” said Dr Wylie, director of the Rocco Ortenzio Neuroimaging Center. “Demonstrating that cognitive fatigue is not task-dependent provides the direction needed to develop effective strategies for managing debilitating cognitive fatigue that severely impacts individuals’ daily functioning and quality of life.”
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