Dataset Information

Perspectives About Time Frames in Stem Cell Research for Multiple Sclerosis: "Time Is Brain".

ABSTRACT:

Background

Stem cell research has been a focus of inquiry in the field of neurology for nearly 3 decades and has led to much hope for people with multiple sclerosis (MS). Previous studies, however, demonstrate that information about the pace of developments in the stem cell arena is less accessible than are representations of potential benefits.

Methods

To explore the understanding and perspectives of adult patients with MS and MS clinicians about the time frames associated with stem cell research, we conducted semistructured interviews with 20 patients with MS across Canada and 15 clinicians who specialize in MS. Patients who participated did not have any previous stem cell interventions. Interviews were analyzed for recurring themes and individual variations using the constant comparative approach.

Results

We found that patients with MS have a limited understanding about the time that it takes for stem cell research to reach the clinic. In parallel, they express a desire to know more than they do about the translational process. Clinicians offer strategies to address patients' questions about the pace of stem cell research and to promote informed hope about experimental interventions.

Conclusions

These results underscore opportunities to promote transparency in clinical discourse about the pace of stem cell research for MS and other progressive neurologic diseases.

SUBMITTER: Benjaminy S

PROVIDER: S-EPMC6709570 | biostudies-literature | 2019 Jul-Aug

REPOSITORIES: biostudies-literature

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Publications

Perspectives About Time Frames in Stem Cell Research for Multiple Sclerosis: "Time Is Brain".

Benjaminy Shelly S Lo Cody C Schepmyer Andrew A Traboulsee Anthony A Illes Judy J

International journal of MS care 20190701 4

<h4>Background</h4>Stem cell research has been a focus of inquiry in the field of neurology for nearly 3 decades and has led to much hope for people with multiple sclerosis (MS). Previous studies, however, demonstrate that information about the pace of developments in the stem cell arena is less accessible than are representations of potential benefits.<h4>Methods</h4>To explore the understanding and perspectives of adult patients with MS and MS clinicians about the time frames associated with s ...[more]

PMID: 31474812

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Project description:Background and objectivesAutologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat aggressive forms of multiple sclerosis (MS). This procedure is believed to result in an immune reset and restoration of a self-tolerant immune system. Immune reconstitution has been extensively studied for T cells, but only to a limited extent for B cells. As increasing evidence suggests an important role of B cells in MS pathogenesis, we sought here to better understand reconstitution and the extent of renewal of the B-cell system after aHSCT in MS.MethodsUsing longitudinal multidimensional flow cytometry and immunoglobulin heavy chain (IgH) repertoire sequencing following aHSCT with BCNU + Etoposide + Ara-C + Melphalan anti-thymocyte globulin, we analyzed the B-cell compartment in a cohort of 20 patients with MS in defined intervals before and up to 1 year after aHSCT and compared these findings with data from healthy controls.ResultsTotal B-cell numbers recovered within 3 months and increased above normal levels 1 year after transplantation, successively shifting from a predominantly transitional to a naive immune phenotype. Memory subpopulations recovered slowly and remained below normal levels with reduced repertoire diversity 1 year after transplantation. Isotype subclass analysis revealed a proportional shift toward IgG1-expressing cells and a reduction in IgG2 cells. Mutation analysis of IgH sequences showed that highly mutated memory B cells and plasma cells may transiently survive conditioning while the analysis of sequence cluster overlap, variable (IGHV) and joining (IGHJ) gene usage and repertoire diversity suggested a renewal of the late posttransplant repertoire. In patients with early cytomegalovirus reactivation, reconstitution of naive and memory B cells was delayed.DiscussionOur detailed characterization of B-cell reconstitution after aHSCT in MS indicates a reduced reactivation potential of memory B cells up to 1 year after transplantation, which may leave patients susceptible to infection, but may also be an important aspect of its mechanism of action.

Project description:BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is highly effective in reducing new inflammatory activity in aggressive multiple sclerosis (MS). A remarkable decrease of serum neurofilament light chains (sNfL) concentration, a marker of axonal damage, was reported in MS following high-intensity regimen AHSCT, but hints for potential neurotoxicity had emerged. sNfL and brain atrophy were therefore analysed in a cohort of patients with aggressive MS treated with intermediate-intensity AHSCT, exploring whether sNfL might be a reliable marker of disability progression independent from new inflammation (i.e. relapses and/or new/gadolinium-enhancing MRI focal lesions).MethodssNfL concentrations were measured using SIMOA methodology in peripheral blood from relapsing-remitting (RR-) or secondary-progressive (SP-) MS patients undergoing AHSCT (MS AHSCT), collected before transplant and at months 6 and 24 following the procedure. sNfL measured at a single timepoint in SP-MS patients not treated with AHSCT without recent inflammatory activity (SP-MS CTRL) and healthy subjects (HD) were used as controls. The rate of brain volume loss (AR-BVL) was also evaluated by MRI in MS AHSCT cases.ResultsThirty-eight MS AHSCT (28 RR-MS; 10 SP-MS), 22 SP-MS CTRL and 19 HD were included. Baseline median sNfL concentrations were remarkably higher in the MS AHSCT than in the SP-MS CTRL and HD groups (p = 0.005 and <0.0001, respectively), and levels correlated with recent inflammatory activity. After a marginal (not significant) median increase observed at month 6, at month 24 following AHSCT sNfL concentrations decreased compared to baseline by median 42.8 pg/mL (range 2.4-217.3; p = 0.039), reducing by at least 50% in 13 cases, and did not differ from SP-MS CTRL (p = 0.110) but were still higher than in HD (p < 0.0001). Post-AHSCT AR-BVL normalised in 55% of RR-MS and in 30% of SP-MS. The effectiveness and safety of AHSCT were aligned with the literature.ConclusionsNfL concentrations correlated with recent inflammatory activity and were massively and persistently reduced by intermediate-intensity AHSCT. Association with response to treatment assessed by clinical or MRI outcomes was not observed, suggesting a good sensitivity of sNfL for recent inflammatory activity but low sensitivity in detecting ongoing axonal damage independent from new focal inflammation.

Dataset Information

Perspectives About Time Frames in Stem Cell Research for Multiple Sclerosis: "Time Is Brain".

Background

Methods

Results

Conclusions

Publications

Perspectives About Time Frames in Stem Cell Research for Multiple Sclerosis: "Time Is Brain".

Similar Datasets

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