2022 Mar 4
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA
Breaking the barriers to remyelination in multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/35255453/
Abstract
Chronically demyelinated axons are rendered susceptible to degeneration through loss of trophic support from oligodendrocytes and myelin, and this process underlies disability progression in multiple sclerosis. Promoting remyelination is a promising neuroprotective therapeutic strategy, but to date, has not been achieved through simply promoting oligodendrocyte precursor cell differentiation, and it is clear that a detailed understanding of the molecular mechanisms underlying failed remyelination is required to guide future therapeutic approaches. In multiple sclerosis, remyelination is impaired by extrinsic inhibitory cues in the lesion microenvironment including secreted effector molecules released from compartmentalized immune cells and reactive glia, as well as by intrinsic defects in oligodendrocyte lineage cells, most notably increased metabolic demands causing oxidative stress and accelerated cellular senescence. Promising advances in our understanding of the cellular and molecular mechanisms underlying these processes offers hope for strategically designed interventions to facilitate remyelination thereby resulting in robust clinical benefits.
Remyelination
Re: Remyelination
https://www.eboro.cz
Re: Remyelination
2024 May 12
Paired vagus nerve stimulation drives precise remyelination and motor recovery after myelin loss
https://pubmed.ncbi.nlm.nih.gov/38766201/
Abstract
Myelin loss in the central nervous system can cause permanent motor or cognitive deficits in patients with multiple sclerosis (MS). While current immunotherapy treatments decrease the frequency of demyelinating episodes, they do not promote myelin repair or functional recovery. Vagus nerve stimulation (VNS) is a neuromodulation therapy which enhances neuroplasticity and the recovery of motor function after stroke, but its effects on myelin repair are not known. To determine if VNS influences myelin repair, we applied VNS following a demyelinating injury and measured longitudinal myelin dynamics and functional recovery. We found that VNS promotes remyelination by increasing the generation of myelinating oligodendrocytes. Pairing VNS with a skilled reach task leads to the regeneration of myelin sheaths on previously myelinated axon segments, enhancing the restoration of the original pattern of myelination. Moreover, the magnitude of sheath pattern restoration correlates with long-term motor functional improvement. Together, these results suggest that recovery of the myelin sheath pattern is a key factor in the restoration of motor function following myelin loss and identify paired VNS as a potential remyelination therapy to treat demyelinating diseases.
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https://www.mayoclinic.org/tests-proced ... c-20384565
Paired vagus nerve stimulation drives precise remyelination and motor recovery after myelin loss
https://pubmed.ncbi.nlm.nih.gov/38766201/
Abstract
Myelin loss in the central nervous system can cause permanent motor or cognitive deficits in patients with multiple sclerosis (MS). While current immunotherapy treatments decrease the frequency of demyelinating episodes, they do not promote myelin repair or functional recovery. Vagus nerve stimulation (VNS) is a neuromodulation therapy which enhances neuroplasticity and the recovery of motor function after stroke, but its effects on myelin repair are not known. To determine if VNS influences myelin repair, we applied VNS following a demyelinating injury and measured longitudinal myelin dynamics and functional recovery. We found that VNS promotes remyelination by increasing the generation of myelinating oligodendrocytes. Pairing VNS with a skilled reach task leads to the regeneration of myelin sheaths on previously myelinated axon segments, enhancing the restoration of the original pattern of myelination. Moreover, the magnitude of sheath pattern restoration correlates with long-term motor functional improvement. Together, these results suggest that recovery of the myelin sheath pattern is a key factor in the restoration of motor function following myelin loss and identify paired VNS as a potential remyelination therapy to treat demyelinating diseases.
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https://www.mayoclinic.org/tests-proced ... c-20384565
https://www.eboro.cz
Re: Remyelination
2024 Jul 4
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada
Loss of miR-145 promotes remyelination and functional recovery in a model of chronic central demyelination
https://pubmed.ncbi.nlm.nih.gov/38965401/
Abstract
Strategies for treating progressive multiple sclerosis (MS) remain limited. Here, we found that miR-145-5p is overabundant uniquely in chronic lesion tissues from secondary progressive MS patients. We induced both acute and chronic demyelination in miR-145 knockout mice to determine its contributions to remyelination failure. Following acute demyelination, no advantage to miR-145 loss could be detected. However, after chronic demyelination, animals with miR-145 loss demonstrated increased remyelination and functional recovery, coincident with altered presence of astrocytes and microglia within the corpus callosum relative to wild-type animals. This improved response in miR-145 knockout animals coincided with a pathological upregulation of miR-145-5p in wild-type animals with chronic cuprizone exposure, paralleling human chronic lesions. Furthermore, miR-145 overexpression specifically in oligodendrocytes (OLs) severely stunted differentiation and negatively impacted survival. RNAseq analysis showed altered transcriptome in these cells with downregulated major pathways involved in myelination. Our data suggest that pathological accumulation of miR-145-5p is a distinctive feature of chronic demyelination and is strongly implicated in the failure of remyelination, possibly due to the inhibition of OL differentiation together with alterations in other glial cells. This is mirrored in chronic MS lesions, and thus miR-145-5p serves as a potential relevant therapeutic target in progressive forms of MS.
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Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada
Loss of miR-145 promotes remyelination and functional recovery in a model of chronic central demyelination
https://pubmed.ncbi.nlm.nih.gov/38965401/
Abstract
Strategies for treating progressive multiple sclerosis (MS) remain limited. Here, we found that miR-145-5p is overabundant uniquely in chronic lesion tissues from secondary progressive MS patients. We induced both acute and chronic demyelination in miR-145 knockout mice to determine its contributions to remyelination failure. Following acute demyelination, no advantage to miR-145 loss could be detected. However, after chronic demyelination, animals with miR-145 loss demonstrated increased remyelination and functional recovery, coincident with altered presence of astrocytes and microglia within the corpus callosum relative to wild-type animals. This improved response in miR-145 knockout animals coincided with a pathological upregulation of miR-145-5p in wild-type animals with chronic cuprizone exposure, paralleling human chronic lesions. Furthermore, miR-145 overexpression specifically in oligodendrocytes (OLs) severely stunted differentiation and negatively impacted survival. RNAseq analysis showed altered transcriptome in these cells with downregulated major pathways involved in myelination. Our data suggest that pathological accumulation of miR-145-5p is a distinctive feature of chronic demyelination and is strongly implicated in the failure of remyelination, possibly due to the inhibition of OL differentiation together with alterations in other glial cells. This is mirrored in chronic MS lesions, and thus miR-145-5p serves as a potential relevant therapeutic target in progressive forms of MS.
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https://www.eboro.cz
Re: Remyelination
2024 Jul 9Petr75 wrote: ↑Wed May 22, 2024 9:20 am 2024 May 12
Paired vagus nerve stimulation drives precise remyelination and motor recovery after myelin loss
https://pubmed.ncbi.nlm.nih.gov/38766201/
Abstract
Myelin loss i....
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https://www.mayoclinic.org/tests-proced ... c-20384565
Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/38968104/
..Together, these data indicate that neuroimmune modulation via VNS may be a promising approach to treat MS, that not only ameliorates symptoms but potentially also promotes myelin repair (remyelination).
https://www.eboro.cz
Re: Remyelination
PIPE-307 trial is about a Clemastine like remyelination agent:
Re: Remyelination
Low intensity repetitive transcranial magnetic stimulation enhances myelin repair in pre-clinical models
-In people living with MS, new and existing myelin-producing cells (oligodendrocytes) can contribute to myelin repair, but current therapies cannot enhance or sustain the natural repair process.
-A non-invasive method called low intensity repetitive transcranial magnetic stimulation (LI-rTMS) can boost the survival of new oligodendrocytes in laboratory models, but it is unclear whether it can promote myelin repair.
-Daily sessions of LI-rTMS were found to increase the amount of myelin produced by oligodendrocytes and enhance myelin repair in laboratory models of MS.
https://www.msaustralia.org.au/news/low ... al-models/
-In people living with MS, new and existing myelin-producing cells (oligodendrocytes) can contribute to myelin repair, but current therapies cannot enhance or sustain the natural repair process.
-A non-invasive method called low intensity repetitive transcranial magnetic stimulation (LI-rTMS) can boost the survival of new oligodendrocytes in laboratory models, but it is unclear whether it can promote myelin repair.
-Daily sessions of LI-rTMS were found to increase the amount of myelin produced by oligodendrocytes and enhance myelin repair in laboratory models of MS.
https://www.msaustralia.org.au/news/low ... al-models/
Baicalin Promotes CNS Remyelination
Demyelinating diseases in the CNS are characterized by myelin sheath destruction or formation disorder that leads to severe neurologic dysfunction. Remission of such diseases is largely dependent on the differentiation of oligodendrocytes precursor cells (OPCs) into mature myelin-forming OLGs at the demyelinated lesions, which is defined as remyelination. We discover that baicalin (BA), a natural flavonoid, in addition to its well-known antiinflammatory effects, directly stimulates OLG maturation and CNS myelin repair.
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https://www.neurology.org/doi/full/10.1 ... 0000001142
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https://www.neurology.org/doi/full/10.1 ... 0000001142
Re: Remyelination
Therapeutic properties of Baicalin –a literature review:
https://osf.io/preprints/osf/2w8y
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https://osf.io/preprints/osf/2w8y
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Re: Remyelination
Current remyelination/neurorestoration/neuroprotection agents in trials:
-NVG-291 (NervGen)
-AntiRGMa - Elezanumab / ABT555 and MT-3291 (AbbVie and Mitsubishi)
-Intermittent Hypoxia (U of Colorado and Spaulding Rehab)
-Nogo Trap / Axer-204 (ReNetX)
-NVG-291 (NervGen)
-AntiRGMa - Elezanumab / ABT555 and MT-3291 (AbbVie and Mitsubishi)
-Intermittent Hypoxia (U of Colorado and Spaulding Rehab)
-Nogo Trap / Axer-204 (ReNetX)