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Secondary resistance to venetoclax in patients with myelodysplastic syndromes (MDS) is not completely elucidated. Here, the authors show that haematopoietic stem cells with a granulo-monocytic differentiation transcriptional state drive secondary resistance to venetoclax in MDS patients who previously failed hypomethylating agent therapy.

2013 witnessed advances in many aspects of multiple sclerosis (MS) research. Two studies highlighted a potential role for salt as an MS trigger, and one immunomodulatory drug performed well in clinical trials. Moreover, treatment effects of MS drugs were shown to correlate inversely with brain atrophy and disease progression.

Using large cohorts from published clinical trials involving more than 8,000 patients with multiple sclerosis, a probabilistic machine learning model reconstructs the transition probabilities from data-derived diseases statuses, showing patterns that suggest how progression to severe stages occur and potential inversion of the process.

Real-world observational studies have the potential to answer questions about multiple sclerosis (MS) treatment that randomized controlled trials cannot. Trojano and colleagues discuss the pitfalls and necessary safeguards in observational studies, and the insights that such studies have provided into treatment decisions for patients with MS.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Early detection of a poor treatment response to disease-modifying agents could be of great benefit to patients with relapsing–remitting multiple sclerosis. Such individuals could be switched to a potentially more effective treatment before too much neurological damage has occurred. In this Review, Río and colleagues examine the use of clinical measures, MRI, and pharmacogenomics in assessing and predicting the treatment response in patients with this condition.

In the 2024 revisions of the McDonald criteria for diagnosis of multiple sclerosis (MS), dissemination in time is no longer required. This paradigm shift is the result of advances in understanding of MS and the development of other biomarkers, enabling earlier diagnosis and treatment that will ultimately improve long-term outcomes.

The IL-1β pathway is upregulated in patients with myelodysplastic syndromes (MDS). Here the authors report the results of a phase 2 clinical trial of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS.

In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group reviews the application of brain and spinal cord atrophy in clinical practice in the management of MS and makes consensus statements and recommendations for future research.

Dendritic cells are specialized antigen-presenting cells that are necessary for inducing immunity and regulating immune tolerance. Understanding how these cells regulate adaptive immune responses has aided the development of a number of novel immunotherapies. In this article, Comabella and colleagues provide an overview of dendritic cell function and evaluate the potential of these therapies to treat multiple sclerosis.

Personalized multiple sclerosis therapy depends on evidence-based prognostication, an initial treatment choice and evaluation of early treatment responses to identify the need to switch therapy. In this Review, Rotstein and Montalban discuss the factors that need to be taken into account to make personalized treatment decisions.

Approximately half of the people currently with multiple sclerosis (MS) are ≥50 years of age, yet guidelines for management of MS in older age are lacking. This Consensus statement presents the outcomes of an International Advisory Committee on Clinical Trials (IACCT) in MS workshop on ageing and MS, including recommendations for advancing research, care and awareness.

Lesion activity detected on MRI scans has become an accepted surrogate for disease activity in relapsing–remitting multiple sclerosis (MS). Barkhof and colleagues provide key recommendations for efficient use of MRI in clinical trials for relapse-onset MS, including practical issues related to acquisition, analysis and reporting of MRI data, approaches to optimization of trial design, and safety considerations.

Shohreh Issazadeh-Navikas and colleagues report on a previously undescribed population of regulatory T (Treg) cells that accumulate in the CNS in response to autoimmune inflammation and are induced by interferon-β (IFN-β). These cells, termed FoxA1+ Treg cells, express the transcription factor FoxA1+, which is required for their development and function. Individuals with multiple sclerosis that respond to IFN-β have an increased frequency of FoxA1+ Treg cells, suggesting that the induction of these cells may account for some of the protective effects of IFN-β.

The use of MRI in patients with multiple sclerosis (MS) is commonplace in clinical settings. However, the precise implementation of MRI in the diagnosis of MS is highly variable, which is problematic in the context of the substantial technical advances of the past decade. In these Evidence-based Guidelines, members of the MAGNIMS study group present a standardized approach to the use of MRI in the diagnosis of MS.

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.

In the second part of the MAGNIMS network's evidence-based guidelines, Wattjes and colleagues discuss the use of MRI in prognostication and follow-up in patients with multiple sclerosis. The group recommend several techniques that are useful for monitoring disease activity and treatment efficacy, and identify those techniques that require further study.