Tysabri (natalizumab) / Biogen, Royalty - LARVOL DELTA

Influence of FCGR2A (rs1801274) and FCGR3A (rs396991) polymorphisms on natalizumab response on multiple sclerosis. (PubMed, Mult Scler Relat Disord) - "The FCGR2A AG and FCGR3A AC genotypes were associated with a lower risk of NTZ treatment failure, suggesting that FcγR polymorphisms may serve as biomarkers for therapeutic response in MS."

Journal • CNS Disorders • Gene Therapies • Inflammation • Multiple Sclerosis • FCGR2A • FCGR3A

Motixafortide (CXCR4 inhibition) alone and in combination with natalizumab (VLA-4 inhibition) to mobilize hematopoietic stem cells for gene therapy in sickle cell disease: A first-in-human, safety and feasibility study (ASH 2025) - P1 | "G-CSF is unsafe inSCD and the CXCR4 inhibitor (CXCR4i) plerixafor (P) does not reliably yield optimal HSC numbers. Remarkably, HSC transplant of non-SCD marrow into SCD mice (myeloablative cKit-ADCconditioning) reverted the enhanced mobilization phenotype in SCD mice to that of non-SCD mice,indicating enhanced CXCR4i-based mobilization in SCD may track with the hematopoietic system.In conclusion, our first-in-human trial demonstrates the potential of M and N+M as novel G-CSF-freeregimens to safely optimize HSC mobilization in SCD (median CD34+ cells/μl: P=73, M=189, N+M=312).Correlative FC and scRNA seq highlight regimen-specific mobilization of unique HSC subsets, includingincreased CLPs, ERPs and MEPs with N+M. Further mechanistic study of HSC mobilization biology maybuild upon our finding that Townes SCD mice and SCD humans share an enhanced mobilizationphenotype with CXCR4i +/- VLA4i."

Clinical • Combination therapy • First-in-human • Gene therapy • P1 data • Dermatology • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Pruritus • Sickle Cell Disease • Urticaria • CD34 • CXCR4

Abnormal adhesion of particular hematopoietic stem and progenitor cell subpopulations in the bone marrow, driven by aberrant interaction between VCAM-1 and VLA-4, ultimately contributes to leukemogenesis (ASH 2025) - "Effects of VLA-4 inhibitionwith natalizumab on these subpopulations were assessed with flow cytometry... The current study demonstrates the contribution of disrupted VCAM-1/VLA-4 interaction toimpaired adhesion of AML MLP and GMP HSPC subpopulations to the bone marrow cellular network.This has led to their exiting the state of dormancy, followed by the loss of stemness, increasedproliferation capacity, higher migration rate and enhanced chemo-resistance, ultimately intensifyingleukemogenesis. Hence, focusing on the preservation of the VCAM-1/VLA-4 interaction in the bonemarrow niche of AML patients could pave the way to a new therapeutic strategy allowing improvedleukemia treatment and relapse prevention."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • VCAM1

Enhanced VLA4-dependent endothelial cell adhesion underpins the higher efficacy of CAR-iNKT over CAR-T cells in limiting leptomeningeal acute leukemia (ASH 2025) - "CAR-T and CAR-iNKT cells had the same levels of beta-1 expression, however only 30% of CAR-T cellsexhibited similar level of alpha-4 expression to CAR-INKT cells (n=5, p < 0.01).To assess the functional role of VLA-4 in CAR-T and CAR-iNKT cells, we measured their adhesion capacityon immobilized soluble VCAM-1 and VCAM-1-expressing HUVEC and BBB-derived hCMEC/D3 endothelialcells, under static and shear stress conditions, either in the presence of natalizumab, an alpha-4 blockingantibody, or its IgG4 isotype...Treatment on day 17, when leukemia cells are readily identified in the meningeal space, showedthat 107 CD19/CD133 CAR-iNKT cells were more effective, compared to same dose CAR T cells, in reducingleukemia burden in the bone marrow, spleen and in near elimination of leukaemia cells in the meningesat 24 hours and even more profoundly at 48 hours post treatment.We conclude that CAR-iNKT cells are inherently better poised than CAR-T cells for treating..."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Multiple Myeloma • Solid Tumor • CD133 • CD28 • ITGA4 • ITGB1 • VCAM1

BH25 Alopecia in a patient undergoing multiple treatments for multiple sclerosis: a rare presentation and case review. (PubMed, Br J Dermatol) - "She was initiated on glatiramer acetate (GA) in 2019...Following this, monthly infusions of natalizumab (eight doses) were administered in 2024...Most recently, she was prescribed cladribine, which caused scalp irritation, including burning and itching a week after each course...Br J Dermatol 2023; 188 (Suppl. 4): ljad113.167]."

Journal • Review • Alopecia • Anorexia • Bulimia • CNS Disorders • Endocrine Disorders • Hematological Disorders • Immunology • Multiple Sclerosis

Towards practical management of the Marburg variant of multiple sclerosis. (PubMed, Mult Scler Relat Disord) - "While no single regimen was uniformly effective, our three-group analysis suggests a stepwise strategy: steroids ± plasma exchange alone were often insufficient; adding a cytotoxic agent with dual B- and T-cell activity (cyclophosphamide or mitoxantrone) was associated with more frequent improvement; and the highest proportion of improvement occurred when dual-arm cytotoxic therapy was combined with a B-cell-directed/lymphocyte-depleting agent."

Journal • CNS Disorders • Multiple Sclerosis • Pediatrics

Selected aspects of epidemiology of multiple sclerosis in Poland: a multicenter pilot study. (PubMed, Neurol Neurochir Pol) - "This study highlights substantial progress in the diagnostic and therapeutic management of MS in Poland over the past 15 years. The widespread implementation of MRI and CSF analysis, alongside significantly improved access to DMTs, has contributed to notably better clinical outcomes. These improvements are reflected in reduced relapse rates, slower disability progression, and a decreased prevalence of secondary progressive MS."

Journal • CNS Disorders • Multiple Sclerosis

Sex differences in multiple sclerosis treatment with disease modifying drugs: a step towards gender neurology. (PubMed, Mult Scler Relat Disord) - "Our results show limited differences in response to DMTs between men and women for the drugs we took into account. Interpretation of these findings is challenging due to limited evidence available about this topic and to sexual dysmorphism involving many aspects of the disease. Small sample size, preventing the analysis of other DMTs (especially high-efficacy ones) and disease courses, is the main limit of this study. Further evidence will be needed in the future."

Journal • CNS Disorders • Multiple Sclerosis • Pulmonary Disease

Natalizumab and fumarate treatment differentially modulate CD4+ T cell and B cell subtypes in multiple sclerosis patients without impacting durable COVID-19 vaccine responses. (PubMed, Front Immunol) - "pwMS treated with natalizumab or fumarates exhibit similarly robust and durable SARS-CoV-2 specific T cell and humoral responses following vaccination and booster dose. DMT-treated pwMS showing comparable responses to healthy individuals following initial vaccination supports the notion that treatment with these specific DMTs does not diminish strong, long-lasting immunity conferred by COVID-19 vaccination, despite the phenotypic differences modulated by each therapy."

Journal • Observational data • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Respiratory Diseases • CD4 • IFNG • IL2

Recent Advances in Interventions Targeting Remyelination and a Systematic Review of Remyelinating Effects of Approved Disease-Modifying Treatments for Multiple Sclerosis. (PubMed, Eur J Neurol) - "Future proof-of-concept clinical trials investigating remyelinating agents in MS should consider combining outcome measures into composite endpoints. Furthermore, research efforts should be dedicated to novel biomarkers to assess repair mechanisms in MS."

Journal • Review • CNS Disorders • Multiple Sclerosis • Solid Tumor

Predictive factors of response to anti-CGRP monoclonal antibodies in patients with multiple sclerosis (EHF-EHC 2025) - "Mainly used DMTs were ocrelizumab (25.5%), natalizumab (19.1%), and dimethyl fumarate (17.0%), while anti-CGRP treatments included anti-CGRP mAbs (95%) and atogepant (5%)...We confirm the safety of combined DMT and CGRP treatments in patients with both conditions. Timely and tailored therapy should be planned early in MS disease course to achieve the best outcomes."

Biomarker • Clinical • CNS Disorders • Migraine • Multiple Sclerosis

Fully-automated estimation of upper cervical cord cross-sectional area using pontomedullary junction referencing in multiple sclerosis. (PubMed, Front Neuroimaging) - "Inclusion criteria were treatment with natalizumab or ocrelizumab and absence of clinical/radiological disease activity over ≥2 years. CSA PMJ measures were negatively associated with disability (β = -0.08, p = 0.002), independent of age and sex. Automated measurement of spinal cord CSA at fixed distance from the PMJ is applicable in MS, performs better than vertebral-based CSA, and correlates with neurological disability."

Journal • CNS Disorders • Multiple Sclerosis

Knowledge Graph-Guided Identification of Multiple Sclerosis and Therapeutic Trend Analysis: Real-World Evidence from Two Large Healthcare Systems. (PubMed, medRxiv) - "Among commonly used standard-effectiveness DMTs, prescriptions for interferon-beta (slope=-0.018±0.011, p<0.001) and glatiramer acetate (slope=-0.013±0.012, p=0.026) and fumarates (slope=-0.031±0.010, p<0.001) declined after 2013...Among commonly used higher-effectiveness DMTs, B-cell depletion therapies (slope=0.051±0.027, p<0.001), particularly ocrelizumab (slope=0.020±0.016, p<0.001), showed a marked increase since 2017. Natalizumab usage peaked in 2012 (slope pre-2012 =0.063±0.012, p pre-2012 <0.001; slope post-2012 =-0.027±0.008, p post-2012 <0.001)...Real-world evidence from two large EHR-based MS cohorts highlights distinct temporal shifts in the MS therapeutic landscape toward higher-effectiveness DMTs, particularly B-cell depletion therapy. Accurate identification of patients diagnosed with multiple sclerosis (MS) from real-world clinical data is essential for tracking longitudinal prescription patterns at..."

HEOR • Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis

Disease-Modifying Treatment Options in Very Early Onset Multiple Sclerosis-What Choices Are There for Onset Under 5 Years of Age? A Systematic Review. (PubMed, J Clin Med) - "Among those treated, acute steroid therapy was administered; 11 received the DMTs interferon, Glatiramer acetate, Dimethyl fumarate, and Azathioprine (three), with only two high-efficacy therapies (Natalizumab and Rituximab). Our patient had partial remission under interferon, relapses when stopped and replaced by immunoglobulin and 9 years relapse-free interval when Natalizumab was introduced. Early treatment with high-efficiency DMTs should be considered in very early POMS; association with known increased neuroplasticity at this age may improve prognosis, allowing good recovery of acquired disability."

Journal • Review • CNS Disorders • Epilepsy • Multiple Sclerosis • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pediatrics

MIGRA-MS: A case series on chronic migraine and multiple sclerosis (EHF-EHC 2025) - "Prior treatments included interferons and glatiramer acetate; current therapies consisted of ocrelizumab, natalizumab, alemtuzumab, teriflunomide, or dimethyl fumarate...All received a median of three classic preventives (amitriptyline in all cases) and onabotulinumtoxinA (PREEMPT, 155 IU) with only one responder; two patients received an extended dose (195 IU) without benefit and later CGRP monoclonal antibodies (galcanezumab, erenumab, eptinezumab) with no response, and atogepant with only transient or partial benefit...In this case series of relapsing–remitting MS with chronic resistant migraine, response to onabotulinumtoxinA and anti-CGRP therapies was limited, with no drug interactions or adverse effects observed. An individualized approach and further studies are needed to assess emerging treatments in this subgroup."

Clinical • CNS Disorders • Migraine • Multiple Sclerosis • Pain

Immune alterations in schizophrenia and the effects of a therapeutic antibody: a neuroimaging study. (PubMed, Brain) - P1 | "We addressed these questions with a baseline case-control comparison of patients with a first-episode psychotic disorder who were symptomatic despite antipsychotic treatment and healthy volunteers, and a longitudinal study testing the effects of natalizumab (a monoclonal antibody previously shown to reduce TSPO levels in neuroinflammatory conditions) on TSPO levels and symptoms in patients...Further work is needed to clarify the functional relevance and cellular specificity of TSPO alterations in psychosis. ClinicalTrials.gov: NCT03093064."

Journal • CNS Disorders • Inflammation • Psychiatry • Schizophrenia

Inflammatory Bowel Disease therapies and Demyelinating Diseases: A Practical Guide to Therapeutic Benefit and Risk. (PubMed, J Crohns Colitis) - "In particular, anti-tumour necrosis factor agents have been consistently linked to new-onset or worsening demyelinating events, while other treatments such as sphingosine-1-phosphate receptor modulators and natalizumab are licensed for both IBD and MS, though real-world data in patients with coexisting disease remain limited...It proposes a practical framework for clinicians, addressing management strategies for patients with confirmed MS, those at increased risk, and individuals who develop neurological symptoms during treatment. In the absence of formal guidelines, multidisciplinary collaboration, early recognition of symptoms, and careful treatment selection are important to optimise both gastrointestinal and neurological outcomes."

Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis • Oncology

Comparative Efficacy of Ublitixumab Versus Natalizumab in the Treatment of Relapsing and Remitting Multiple Sclerosis. (PubMed, Cureus) - "Among these, monoclonal antibodies such as ublituximab and natalizumab have emerged as key therapeutic options with distinct mechanisms of action and safety profiles. This narrative review aims to compare the efficacy, safety, and clinical impact of ublituximab and natalizumab in the treatment of RRMS, providing insights into their role in individualized treatment strategies."

Journal • Review • CNS Disorders • Immunology • Multiple Sclerosis

LPX-TI641, a Tim3/4 Agonist, Induces Long-Term Immune Tolerance in Multiple Sclerosis Models. (PubMed, Pharmaceutics) - "Efficacy in animal models was comparable to or exceeded that of high-efficacy DMTs, including natalizumab. LPX-TI641 promotes antigen-independent immune tolerance through Tim receptor agonism and Treg expansion. These findings support its potential as a novel therapeutic candidate for MS, addressing the limitations of current DMTs."

Journal • CNS Disorders • Immunology • Multiple Sclerosis • CD4 • FOXP3 • HAVCR2

Long-term progressive multifocal leukoencephalopathy risk stratification in multiple sclerosis patients treated with natalizumab with positive John Cunningham virus index. (PubMed, Neurol Neurochir Pol) - "Natalizumab can be used for long-term treatment of patients with MS even with positive JCV index if recommended precautions such as EID and frequent brain MRIs are followed."

Journal • CNS Disorders • Multiple Sclerosis • Rare Diseases

Bridging pharmacovigilance and genetic insight: investigating drugs and indications for breast cancer risk in women with autoimmune diseases. (PubMed, J Transl Med) - "Our study uncovered several immune-related drugs associated with increased breast cancer reporting in women with AIDs. This risk may be explained by several potential drug targets with causal roles, or by the shared genetic comorbidity between specific AIDs and breast cancer. These insights emphasize the need for tailored breast cancer surveillance and highlight potential molecular targets for intervention in vulnerable populations."

Adverse events • Journal • Breast Cancer • CNS Disorders • Diabetes • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Metabolic Disorders • Migraine • Oncology • Pain • Solid Tumor • Type 1 Diabetes Mellitus • Ulcerative Colitis • CALCRL • CENPO • PARP1

Real-world evaluation of subcutaneous natalizumab in patients with highly active relapsing-remitting multiple sclerosis. (PubMed, Mult Scler Relat Disord) - "This real-world analysis demonstrates that SC natalizumab is a highly effective and safe treatment for patients with highly active RRMS. The observed clinical and radiological stability supports the use of SC natalizumab as a viable and convenient alternative to IV administration, aligning with outcomes from pivotal clinical trials."

HEOR • Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis

Safety of disease-modifying therapies in multiple sclerosis: real-world data from the Austrian MS Treatment Registry (AMSTR). (PubMed, J Neurol) - "The safety data from the AMSTR do not reveal any new safety issues, particularly regarding neoplasms and infections. Hence, people with MS as well as their treating neurologists are reassured to continue treatment with DMT, as the benefit-risk profile of DMT could be reaffirmed."

Journal • Real-world evidence • Basal Cell Carcinoma • CNS Disorders • Endocrine Disorders • Infectious Disease • Multiple Sclerosis • Non-melanoma Skin Cancer • Oncology

Comparative evaluation of STRATIFY JCV™ and IMMUNOWELL™ assays for anti-JCV antibody detection in natalizumab-treated RRMS patients. (PubMed, Ther Adv Neurol Disord) - "IMMUNOWELL may serve as a reliable complementary method, especially in cases where borderline serostatus could influence therapeutic strategy. Regular and accurate monitoring of JCV status remains essential for guiding long-term treatment safety and optimizing individual patient outcomes."

Journal • CNS Disorders • Multiple Sclerosis

Wearing-off symptoms persist in the majority of patients with multiple sclerosis after switching from natalizumab to ocrelizumab. (PubMed, J Neurol Sci) - "These findings could be valuable for patient counselling, though validation in a larger cohort is desired."

Journal • CNS Disorders • Multiple Sclerosis