Teriflunomide treatment is associated with optic nerve recovery in early multiple sclerosis

Pfeuffer, Steffen; Kerschke, Laura; Ruck, Tobias; Rolfes, Leoni; Pawlitzki, Marc; Albrecht, Philipp; Wiendl, Heinz; Meuth, Sven G.

doi:10.1177/1756286421997372

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…However, a previous study revealed teriflunomide to impair microglial activation in a mutant PLP mouse model [ 26 ], indicating that also resident immune cells are tamed further contributing to an overall beneficial effect. Accordingly, a recent clinical study indicated that teriflunomide treatment is associated with favorable outcomes regarding functional optic nerve recovery following optic neuritis in early multiple sclerosis [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Teriflunomide as a therapeutic means for myelin repair

Göttle

Groh

Reiche

et al. 2023

J Neuroinflammation

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Background Promotion of myelin repair in the context of demyelinating diseases such as multiple sclerosis (MS) still represents a clinical unmet need, given that this disease is not only characterized by autoimmune activities but also by impaired regeneration processes. Hence, this relates to replacement of lost oligodendrocytes and myelin sheaths—the primary targets of autoimmune attacks. Endogenous remyelination is mainly mediated via activation and differentiation of resident oligodendroglial precursor cells (OPCs), whereas its efficiency remains limited and declines with disease progression and aging. Teriflunomide has been approved as a first-line treatment for relapsing remitting MS. Beyond its role in acting via inhibition of de novo pyrimidine synthesis leading to a cytostatic effect on proliferating lymphocyte subsets, this study aims to uncover its potential to foster myelin repair. Methods Within the cuprizone mediated de-/remyelination model teriflunomide dependent effects on oligodendroglial homeostasis and maturation, related to cellular processes important for myelin repair were analyzed in vivo. Teriflunomide administration was performed either as pulse or continuously and markers specific for oligodendroglial maturation and mitochondrial integrity were examined by means of gene expression and immunohistochemical analyses. In addition, axon myelination was determined using electron microscopy. Results Both pulse and constant teriflunomide treatment efficiently boosted myelin repair activities in this model, leading to accelerated generation of oligodendrocytes and restoration of myelin sheaths. Moreover, teriflunomide restored mitochondrial integrity within oligodendroglial cells. Conclusions The link between de novo pyrimidine synthesis inhibition, oligodendroglial rescue, and maintenance of mitochondrial homeostasis appears as a key for successful myelin repair and hence for protection of axons from degeneration.

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Section: Discussionmentioning

confidence: 99%

Teriflunomide as a therapeutic means for myelin repair

Göttle

Groh

Reiche

et al. 2023

J Neuroinflammation

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“…iii) Secondary progressive MS (SPMS): This type follows RRMS, but with more severe symptoms. iv) Progressive relapsing MS (PRMS): In this type, symptoms worsen from the beginning with periods of remission ( 4 , 5 ).…”

Section: Categories Of Multiple Sclerosismentioning

confidence: 99%

Unleashing nature's potential and limitations: Exploring molecular targeted pathways and safe alternatives for the treatment of multiple sclerosis (Review)

Fathallah,

Abdellatif,

Saadeldin

2023

Med Int

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Driven by the limitations and obstacles of the available approaches and medications for multiple sclerosis (MS) that still cannot treat the disease, but only aid in accelerating the recovery from its attacks, the use of naturally occurring molecules as a potentially safe and effective treatment for MS is being explored in model organisms. MS is a devastating disease involving the brain and spinal cord, and its symptoms vary widely. Multiple molecular pathways are involved in the pathogenesis of the disease. The present review showcases the recent advancements in harnessing nature's resources to combat MS. By deciphering the molecular pathways involved in the pathogenesis of the disease, a wealth of potential therapeutic agents is uncovered that may revolutionize the treatment of MS. Thus, a new hope can be envisioned in the future, aiming at paving the way toward identifying novel safe alternatives to improve the lives of patients with MS.

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