The latest research on multiple sclerosis: insights from Nature journals
Nature journals are among the leading sources of scientific information on MS, covering various aspects of the disease from basic immunology to clinical trials. In this article, we will summarize some of the recent articles on MS published in Nature journals, highlighting their main findings and implications for the field.
How inflammation affects remyelination and disease progression in MS
Remyelination is the process of repairing damaged myelin sheaths that surround and protect nerve fibers in the CNS. Remyelination is essential for restoring neuronal function and preventing further neurodegeneration in MS. However, remyelination often fails or is insufficient in MS, leading to chronic demyelination and axonal loss.
In a review article published in Nature Reviews Neurology, Klotz et al. discuss how inflammation affects remyelination and disease progression in MS. They summarize the current knowledge on the cellular and molecular mechanisms of remyelination and remyelination failure in MS, focusing on the roles of different immune cells and cytokines. They also review the potential therapeutic strategies to enhance remyelination and reduce inflammation in MS, such as targeting specific immune pathways, modulating the extracellular matrix, or promoting endogenous or exogenous stem cell differentiation into oligodendrocytes, the cells that produce myelin.
The authors conclude that inflammation has both beneficial and detrimental effects on remyelination in MS, depending on the timing, location, and intensity of the inflammatory response. They suggest that a better understanding of the factors that regulate inflammation and remyelination in MS could lead to more effective treatments that can halt or reverse disease progression.
Reference: Klotz L., Antel J., Kuhlmann T. Inflammation in multiple sclerosis: consequences for remyelination and disease progression. Nat Rev Neurol. 2023;19(4):217-232.
How Bruton tyrosine kinase inhibitors can treat MS
Bruton tyrosine kinase (BTK) is an enzyme that is involved in the activation and survival of B cells, which are immune cells that produce antibodies and contribute to inflammation and tissue damage in MS. BTK inhibitors are a class of drugs that block the activity of BTK, thereby reducing B cell function and modulating other immune cells.
In another review article published in Nature Reviews Neurology, Krämer et al. examine the potential of BTK inhibitors for treating MS. They describe the biological rationale for targeting BTK in MS, based on the evidence from animal models and human studies. They also discuss the clinical development and outcomes of different BTK inhibitors for MS, such as evobrutinib, fenebrutinib, pirtobrutinib, and tolebrutinib. They compare the efficacy, safety, pharmacokinetics, pharmacodynamics, and biomarkers of these drugs across different phases of clinical trials.
The authors conclude that BTK inhibitors are an emerging treatment option for MS, showing promising results in reducing relapse rate, lesion activity, and disability progression in patients with relapsing-remitting or primary progressive forms of MS. They also highlight some of the challenges and opportunities for further research on BTK inhibitors for MS, such as optimizing dosing regimens, identifying predictors of response or resistance, assessing long-term safety and efficacy, and exploring combination therapies with other drugs.
Reference: Krämer J., Bar-Or A., Wiendl H. Bruton tyrosine kinase inhibitors for multiple sclerosis. Nat Rev Neurol. 2023;19(4):233-246.
How T cell-microbiome communication influences disease in an MS model
The microbiome is the collection of microorganisms that live in and on our body, especially in the gut. The microbiome can influence various aspects of our health and disease, including our immune system. Several studies have shown that alterations in the microbiome composition or function are associated with MS risk or severity.
In a research highlight published in Nature Reviews Neurology, Lemprière summarizes a new study by Wang et al. that investigates how T cell-microbiome communication influences disease in an animal model of MS, called experimental autoimmune encephalomyelitis (EAE). The study shows that T cells can directly sense and respond to microbial metabolites in the gut, such as short-chain fatty acids (SCFAs), which modulate their differentiation and function. The study also shows that T cells can indirectly affect the microbiome composition and function by secreting cytokines that alter the gut environment. The study demonstrates that manipulating T cell-microbiome communication by administering SCFAs or anti-cytokine antibodies can ameliorate or exacerbate EAE, respectively.
The author highlights the importance of this study for understanding the bidirectional interaction between T cells and the microbiome in MS, and the potential of targeting this interaction for therapeutic purposes.
Reference: Lemprière S. T cell–microbiome communication influences disease in MS model. Nat Rev Neurol. 2023;19(3):131.
How Epstein-Barr virus may cause MS
Epstein-Barr virus (EBV) is a common herpesvirus that infects most people during their lifetime, usually causing mild or asymptomatic infections. However, EBV has also been implicated in the development of several diseases, including MS. Several lines of evidence suggest that EBV infection is a necessary but not sufficient factor for MS pathogenesis, such as the high prevalence of EBV seropositivity among MS patients, the association of EBV infection with increased MS risk, and the presence of EBV-infected B cells in MS lesions.
In a review article published in Nature Reviews Neurology, Bjornevik et al. provide an overview of the evidence indicating that MS is a rare complication of EBV infection. They discuss the possible mechanisms by which EBV may trigger or sustain MS, such as molecular mimicry, bystander activation, epitope spreading, chronic inflammation, or direct infection of CNS cells. They also review the potential strategies to prevent or treat MS by targeting EBV, such as vaccination, antiviral drugs, or immunotherapy.
The authors conclude that EBV is a leading cause of MS, and that further research is needed to elucidate the exact role and timing of EBV infection in MS development and progression. They suggest that targeting EBV may offer a novel and effective way to prevent or cure MS.
Reference: Bjornevik K., Münz C., Ascherio A. Epstein–Barr virus as a leading cause of multiple sclerosis: mechanisms and implications. Nat Rev Neurol. 2023;19(2):75-88.
How cholesterol pathway is associated with MS disability
Cholesterol is a lipid molecule that is essential for various biological functions, such as membrane structure, hormone synthesis, and signal transduction. However, cholesterol metabolism can also have detrimental effects on health and disease, such as cardiovascular disease, diabetes, and neurodegenerative disorders.
In a brief report published in Nature Reviews Neurology, Kiani summarizes a new study by Wang et al. that investigates the association between cholesterol pathway and MS disability. The study analyzes the genetic variants and gene expression data from more than 10,000 MS patients and healthy controls, focusing on genes involved in cholesterol biosynthesis, transport, and degradation. The study identifies several genetic variants and gene expression changes in the cholesterol pathway that are associated with increased risk or severity of MS. The study also shows that some of these genetic variants affect the levels of cholesterol metabolites in the blood or cerebrospinal fluid of MS patients.
The author highlights the significance of this study for revealing new insights into the role of cholesterol pathway in MS pathophysiology and progression. The author also suggests that modulating cholesterol metabolism may be a potential therapeutic strategy for MS.
Reference: Kiani L. Cholesterol pathway associated with MS disability. Nat Rev Neurol. 2022;18(1):5