Radiologically isolated syndromes: to treat or not to treat?

Preziosa, Paolo; Rocca, Maria A.; Filippi, Massimo

doi:10.1007/s00415-024-12294-4

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…Additionally, radiologically isolated syndrome (RIS) patients may show no apparent neurological symptoms but display MRI signs of ongoing demyelination in the CNS [ 41 ]. Identified risk factors for the occurrence of a first clinical event in RIS patients include specific lesion patterns (the presence of infratentorial, spinal cord, or gadolinium-enhancing lesions) and cerebrospinal fluid-specific oligoclonal bands [ 42 ]. The presence of cerebrospinal fluid-specific oligoclonal bands is associated with a higher risk of progression from CIS and RIS to MS, underscoring the importance of humoral autoimmune processes in the initial stages of MS.…”

Section: Clinical Considerationsmentioning

confidence: 99%

“…Developing new technologies for pre-symptomatic subjects or patients with mild, early-stage clinical symptoms necessitates accurately identifying high-risk subgroups expected to experience rapid disease progression. It is crucial to demonstrate an acceptable benefit–risk ratio based on the cost-effectiveness of a technology and its impact on healthcare budgets [ 42 ]. Identifying high-risk subgroups with high specificity and similar pathomechanisms may also enable defining new orphan conditions and guide the development of disease-stopping technologies, including tailored curative cell therapies.…”

Section: Clinical Considerationsmentioning

confidence: 99%

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Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront

Pitter,

Nagy,

Nagy

et al. 2024

JPM

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Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments.

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Section: Clinical Considerationsmentioning

confidence: 99%

Section: Clinical Considerationsmentioning

confidence: 99%

Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront

Pitter,

Nagy,

Nagy

et al. 2024

JPM

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Global transcriptome profiling of blood mononuclear cells from individuals with radiologically isolated syndrome reveals abnormalities characteristic of the rapid manifestation of multiple sclerosis symptoms

Kozin,

Kabaeva,

Omarova

et al. 2024

RJTAO

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Objective: to look for differences in the transcriptome profiles in mononuclear blood cells of a group of patients with radiologically isolated syndrome (RIS) who developed symptoms of multiple sclerosis (MS) in the following three years of observation and a group of patients with RIS who did not develop MS during this period.Material and methods. The study included 19 patients with RIS (9 men and 10 women), six of whom developed symptoms of MS during the three-year follow-up period. The transcription profiles of blood mononuclear cells were compared between the groups of patients with RIS who developed or did not develop MS symptoms during this period. The work was conducted in the format of a prospective study; the time of blood collection was taken as the reference point. Full transcriptome profiling was performed using RNA sequencing on an MGISEQ-200 platform. Differential gene expression analysis was performed using the DESeq2 package for the R programming language. Subsequent analysis involved constructing a network of interactions between the protein products of the detected differentially expressed genes based on data from the STRING database, identifying a cluster of interacting proteins, and analyzing the enrichment of this cluster by participants in pathways annotated in the KEGG database.Results. The expression of 146 genes differed significantly (p<0.05; |log2FC| >1) in the studied groups of patients with RIS: in patients with subsequent manifestation of MS symptoms, the expression of 67 genes was lower and expression of 79 genes was higher than in patients without MS symptoms. The decrease in expression of two of the 67 genes (ADGRG7 and LGALS9C) remained significant even after correction for multiple comparisons (padj=2.17⋅10-11 and padj=6.19⋅10-6, respectively). Analyzing the network of interactions between the protein products of the differentially expressed genes allowed the identification of a cluster of 12 genes: APBB2, CCL4, CCL4L2, CDH2, DAZL, FOSB, H2BC17, JUN, KLF4, KLF5, MAPK8IP1, SYCE1; it is over-represented by components of the Toll-like receptor signaling pathway.Conclusion. The transcriptome profiles of blood mononuclear cells differ in groups of patients with RIS who did or did not develop MS symptoms during the three-year follow-up period. The decrease in the expression level of ADGRG7 and LGALS9C genes detected in this study as a sign of rapid conversion of RIS to MS needs to be confirmed in independent samples.

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Radiologically isolated syndromes: to treat or not to treat?

Cited by 2 publications

References 47 publications

Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront

Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront

Global transcriptome profiling of blood mononuclear cells from individuals with radiologically isolated syndrome reveals abnormalities characteristic of the rapid manifestation of multiple sclerosis symptoms

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