Blood neurofilament light chain at the doorstep of clinical application

Multiples sclerosis (MS) is a chronic progressive disorder of the CNS with inflammatory and neurodegenerative pathomechanisms leading to various degrees of neurologic disability. In the past 2 decades, high-efficacy disease-modifying therapies (DMTs) have become available that lead to near-complete suppression of acute disease activity (relapses, lesion formation) in most patients, and only a small number of patients exhibit an aggressive disease course despite adequate use of DMTs. Here, immunoablation followed by stem cell transplantation (SCT) has emerged in recent years as an efficacious approach to stop acute disease activity, based on the concept of a reset of the immune system. However, DMTs show minimal effect on the course of progression. Accordingly, 30% (7/23) of patients continue to experience clinical progression and additional brain atrophy as its MRI equivalent 12 months after SCT.1
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Clinical trials Observational study (Cohort, Case control), Class II, Multiple sclerosis Editorial Source Type: research

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ABSTRACT Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Its treatment has focused on inflammation control as early as possible to avoid disability. Autologous hematopoietic stem cell transplantation (AHSCT) has been used for treating MS since 1996, with recent decisive results regarding benefits in long-term efficacy. Five patients followed up at an MS center in Belo Horizonte, Brazil, who had relapsing-remitting MS with high disease activity, underwent AHSCT between 2009 and 2011. They were evaluated clinically, with magnetic resonance imaging, and by the EDSS every six months after t...
Source: Arquivos de Neuro-Psiquiatria - Category: Neurology Source Type: research
Objective To evaluate neurofilament light chain (NfL) levels in serum and CSF of patients with aggressive MS pre- and post-treatment with immunoablation followed by autologous hematopoietic stem cell transplantation (IAHSCT) and examine associations with clinical and MRI outcomes. Methods Paired serum and CSF in addition to MRI and clinical measures were collected on 23 patients with MS at baseline and 1 and 3 years post-IAHSCT. An additional 33 sera and CSF pairs were taken from noninflammatory neurologic controls. NfL levels were quantitated using the Simoa platform (Quanterix). Results Baseline MS NfL levels were sign...
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Clinical trials Methodology/study design, Clinical trials Observational study (Cohort, Case control), Class II, Multiple sclerosis Article Source Type: research
CONCLUSIONS: Changes in the self-reported EDSS score in parallel with neurological improvement, were observed in persons with all types of MS after HSCT, employing the "Mexican method". This article is protected by copyright. All rights reserved. PMID: 31394007 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research
This study shows that mRNA levels of the aging related lamin A splice variant progerin, associated with premature aging in HGPS, were significantly upregulated in subjects with BMI ≥ 25 kg/m2. Moreover, our data revealed a significantly positive correlation of BMI with progerin mRNA. These data provide to our knowledge for the first-time evidence for a possible involvement of progerin in previously observed accelerated aging of overweight and obese individuals potentially limiting their longevity. Our results also showed that progerin mRNA was positively correlated with C-reactive protein (CRP). This might suggest an as...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Whereas drugs used for maintenance/escalation therapy do not maintain their beneficial effect after cessation of therapy, some new highly effective therapies can show prolonged treatment effects after a short treatment course. Such therapies have been named pulsed immune reconstitution therapies or pulsed immunosuppressive therapies, and typical representatives are alemtuzumab and cladribine. Autologous haematopoietic stem cell transplantation could be considered as the strongest immune reconstitution therapy. Both alemtuzumab and cladribine induce depletion of lymphocytes, and a common mechanism of actio...
Source: Herpes - Category: Infectious Diseases Authors: Tags: Ther Adv Neurol Disord Source Type: research
Multiple sclerosis (MS) is an autoimmune disorder that typically affects young people during their most productive years, causing irreversible damage and accumulation of disability. Treatments over time have had modest effects at completely controlling or suppressing disease activity, but are generally aimed at controlling early dominating inflammation that, over time, accumulates damage and leads to progressive disability. Some unfortunate patients are destined to deteriorate despite even newer and more effective agents because of the inability of these drugs to fully curb the inflammatory component of the disease. These ...
Source: Cold Spring Harbor perspectives in medicine - Category: Research Authors: Tags: Multiple Sclerosis PERSPECTIVES Source Type: research
In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
For more than twenty years now, Richard Burt's research teams have been working on the treatment of autoimmunity through the destruction and recreation of the immune system. Autoimmunity is a malfunction in the self-tolerance of immune cells, leading them to attack patient tissues. The malfunction is entirely contained in the immune system, so if the immune system is destroyed and replaced, the autoimmunity stops. If the genesis of autoimmunity is happenstance, an unfortunate one-time accident, then this is a cure. But if autoimmunity has a trigger outside the immune system in a given patient, it will return after some per...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Multiple sclerosis (MS) is an autoimmune disease that results from breakdown of immunological tolerance toward the central nervous system. The early course of MS is commonly characterized by repeated acute episodes of focal inflammation within the central nervous system causing neurologic events called relapses, characterized by the development of neurological disabilities and gadolinium-enhancing and demyelinating lesions on magnetic resonance imaging (MRI) scans. As the acute inflammation resolves over the course of several weeks, neurologic symptoms may partially or completely resolve. Over time, these acute inflammator...
Source: JAMA - Category: General Medicine Source Type: research
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