Article
|
Open Access
Featured
-
-
Article
| Open AccessElevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
Analysis of a large ancient genome dataset shows that genetic risk for multiple sclerosis rose in steppe pastoralists, providing insight into how genetic ancestry from the Neolithic and Bronze Age has shaped modern immune responses.
- William Barrie
- , Yaoling Yang
- & Eske Willerslev
-
Article |
Locus for severity implicates CNS resilience in progression of multiple sclerosis
A genome-wide association study including 22,389 cases of multiple sclerosis finds an association with disease progression at the DYSF–ZNF638 and DNM3–PIGC loci and identifies a potential of higher educational attainment in slowing disease progression.
- Adil Harroud
- , Pernilla Stridh
- & Kári Stefánsson
-
Article
| Open AccessTwin study reveals non-heritable immune perturbations in multiple sclerosis
In monozygotic twins discordant for multiple sclerosis, the influence of genetic predisposition and environmental factors is determined using matched-pair analyses.
- Florian Ingelfinger
- , Lisa Ann Gerdes
- & Burkhard Becher
-
Article |
Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM
The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.
- Tobias V. Lanz
- , R. Camille Brewer
- & William H. Robinson
-
Article |
A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis
Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis.
- Martina Absinta
- , Dragan Maric
- & Daniel S. Reich
-
Article |
Neuronal vulnerability and multilineage diversity in multiple sclerosis
Single-cell RNA sequencing was used to construct a map of gene expression in lesions from brains of patients with multiple sclerosis, revealing distinct lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation.
- Lucas Schirmer
- , Dmitry Velmeshev
- & David H. Rowitch
-
Letter |
Altered human oligodendrocyte heterogeneity in multiple sclerosis
Single-nucleus RNA sequencing analysis identifies different subclusters of oligodendroglia in white matter from individuals with multiple sclerosis compared with controls, and these differences may be important for understanding disease progression.
- Sarah Jäkel
- , Eneritz Agirre
- & Gonçalo Castelo-Branco
-
Letter |
Dynamics of oligodendrocyte generation in multiple sclerosis
There are no new oligodendrocytes in potentially remyelinated multiple sclerosis shadow plaques, although oligodendrocyte generation is increased in the normal appearing white matter of patients with aggressive disease, informing the development of new therapies.
- Maggie S. Y. Yeung
- , Mehdi Djelloul
- & Jonas Frisén
-
Letter |
Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination
Many small molecules that stimulate oligodendrocyte formation act not through their canonical pathways but by inhibiting enzymes within the cholesterol biosynthesis pathway and thereby inducing the accumulation of 8,9-unsaturated sterols.
- Zita Hubler
- , Dharmaraja Allimuthu
- & Drew J. Adams
-
Article |
Salt-responsive gut commensal modulates TH17 axis and disease
High salt intake changed the gut microbiome and increased TH17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of TH17 cells and increased blood pressure in humans.
- Nicola Wilck
- , Mariana G. Matus
- & Dominik N. Müller
-
Letter |
Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia
Ischaemia damages nerve myelin by depriving neurons and their myelinating oligodendrocytes of oxygen and glucose; here it is shown that ischaemic damage is caused through the H+-dependent activation of TRPA1 channels, and not via glutamate receptors of the NMDA type, as previously thought, providing a new mechanism and promising therapeutic targets for diseases as diverse and prevalent as cerebral palsy, spinal cord injury, stroke and multiple sclerosis.
- Nicola B. Hamilton
- , Karolina Kolodziejczyk
- & David Attwell
-
News & Views |
Licensed in the lungs
In multiple sclerosis, the body's own immune cells attack the brain and spinal cord. But how they get there from peripheral tissues has been a mystery. Surprisingly, the lungs might be a key transit point. See Letter p.675
- Richard M. Ransohoff
-
News |
Genome study highlights risk factor for multiple sclerosis
Discovery of genetic variant could help to improve clinical trials of potential therapies.
- Ewen Callaway
-
Letter |
TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis
Genome-wide association studies in combination with functional analyses identify a genetic variant that explains why anti-tumour necrosis factor therapy, used in several autoimmune diseases, exacerbates multiple sclerosis.
- Adam P. Gregory
- , Calliope A. Dendrou
- & Lars Fugger
-
-
Outlook |
Animal models: Not close enough
Despite some outstanding drug-development successes, the mouse version of multiple sclerosis has been worryingly unreliable at screening human treatments.
- Jocelyn Rice
-
Outlook |
Perspective: Let the sunshine in!
Population and genetic studies are confirming the link between multiple sclerosis and vitamin D, says Richard Ransohoff.
- Richard M. Ransohoff
-
Outlook |
Progressive multiple sclerosis: The treatment gap
Most new treatments for multiple sclerosis are for patients with the relapsing–remitting form of the disease. Those with the more advanced, progressive type are being left behind.
- Courtney Humphries
-
Outlook |
Diagnostics: Getting a clear picture
Technologies that better reveal the insidious progression of multiple sclerosis could aid the search for treatments.
- Cynthia Graber
-
Outlook |
Aetiology: The X factor
Researchers have plenty of theories about what might cause multiple sclerosis. But for now, the factor that triggers the disease remains elusive.
- Lauren Gravitz
-
Outlook |
Genomics: A complex code
More than 100 variations in the genome have been linked to multiple sclerosis. Researchers are now trying to find the overlap with other auto-immune conditions, and understand how environmental factors interact with genes to trigger disease.
- Virginia Hughes
-
Outlook |
Perspective: Deconstructing a disease
A slew of new data suggests that it is time to rethink and reclassify autoimmune disease, says David A. Hafler.
- David A. Hafler
-
Outlook |
Alternative therapies: Desperate measures
Worms? Stents? Bee stings? Patients with multiple sclerosis who exhaust conventional therapies are turning in desperation to unproven approaches.
- Jennifer Berglund
-
Outlook |
Stem cells: Don't believe the hype
Researchers are still a long way from using stem cells to halt the decline caused by multiple sclerosis and to restore patients' health. But they are following some promising trails.
- Michael Eisenstein
-
Outlook |
Drugs: An injection of hope
For decades, drugs have barely managed to slow the progression of multiple sclerosis. Therapies are now emerging that may even help to reverse the disease — but are they worth the risk?
- Duncan Graham-Rowe
-
Research Highlights |
A boost to the brain's barrier
-
News |
Antibody offers hope for multiple sclerosis treatment
Promising phase III trial paves the way for alemtuzumab approval.
- Duncan Graham-Rowe
-
News & Views |
One protein, two healing properties
Multiple sclerosis is linked to rogue immune cells that attack mature neurons. Remarkably, immature neurons secrete a protein called LIF, which not only inhibits this attack, but also promotes repair of the damaged nerves.
- Su M. Metcalfe
-
Letter |
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- Stephen Sawcer
- , Garrett Hellenthal
- & Alastair Compston
-
Research Highlights |
Protein brings death to myelin
-
Comment |
The rise of people power
Calls in Canada for trials of a contentious treatment for multiple sclerosis illustrate how social media can affect research priorities, say Roger Chafe and his colleagues.
- Roger Chafe
- , Karen B. Born
- & Andreas Laupacis
-
Research Highlights |
Neuroimmunology: Autoimmune disease culprit
-
Research Highlights |
Immunology: Killer cells help
-
News |
Twin study surveys genome for cause of multiple sclerosis
Mapping milestone emphasizes complexity of disease.
- Alla Katsnelson
-
Letter
| Open AccessGenome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis
Studies of identical twins are widely used to dissect the contributions of genes and the environment to human diseases. In multiple sclerosis, an autoimmune demyelinating disease, identical twins often show differences. This might suggest that environmental effects are most significant in this case, but genetic and epigenetic differences between identical twins have been described. Here, however, studies of identical twins show no evidence for genetic, epigenetic or transcriptome differences that could explain disease discordance.
- Sergio E. Baranzini
- , Joann Mudge
- & Stephen F. Kingsmore
-
News & Views |
Closing in on an oral treatment
At present, only injectable drugs are available for treating multiple sclerosis. So clinical trials indicating that the drug fingolimod might be a step towards an oral treatment for the disease are exciting indeed.
- Roland Martin