Repurposing multiple sclerosis drugs: a review of studies in neurological and psychiatric conditions

Sellner, Johann

doi:10.1016/j.drudis.2019.05.009

Cited by 9 publications

(7 citation statements)

References 50 publications

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“…3 Experimental autoimmune encephalomyelitis (EAE), the animal model of MS which is most commonly used to study the underlying mechanism, provides a theoretical basis for developing novel therapies for MS. 4 Treatment options for MS have been improved in the past 20 years, with the increased availability of new oral disease-modifying drugs and monoclonal antibodies. 5 Nevertheless, there remains a number of unmet needs in the management of MS that should be approached with novel experimental therapies, such as those that target the main pathogenic mechanisms with high specificity and, ideally, restore the defective immune response without altering the 'normal' functions of the immune system. Accumulation of oligodendrocyte progenitor cells (OPCs) has been frequently observed in CNS demyelinated lesions in MS patients and EAE mice.…”

Section: Introductionmentioning

confidence: 99%

Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Tian

Xiao

et al. 2022

Nanoscale

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Section: Introductionmentioning

confidence: 99%

Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Tian

Xiao

et al. 2022

Nanoscale

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“…Inflammation in MS is considered to be mostly driven by T-cells; however, with the introduction of B-cell depleting therapeutic agents, there is increasing evidence for CD20-expressing T-and B-cells as the second pillar in the pathogenesis of MS [5,6]. Immunotherapies have been widely used in MS, as they have been shown to reduce the relapse rate and the accumulation of new brain lesions in patients with relapsing-remitting MS (RRMS) [7,8]. In recent years, vitamin D was brought into focus as it is suspected to play an important part in the pathogenesis of MS. Several studies have been conducted to ascertain its presumed protective effects and its ability to decrease the risk of MS, disease activity and progression.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

et al. 2020

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

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“…17,97,[150][151][152][153] Vitamin D is a modulator of the immune system, 154,155 hence its mention here, and accumulating evidence suggests vitamin D deficiency is a risk factor for dysregulated Klotho-associated neurodegenerative diseases, the most noteworthy being MS. 9,27,52,97,102,150,152,153,[156][157][158] Multiple Sclerosis MS is an insidious progressive neurodegenerative disease characterized by demyelinated lesions throughout the brain, spinal cord, and optic nerve resulting from immune-mediated attacks against myelin. [159][160][161][162][163][164][165] It is the apotheosis of myelination disorders that affects *2.5 million people around the world [166][167][168] and currently there are no definitive cures. The standard of chronic care, after using steroids for acute episodes, centers on the use of disease modifying therapies (DMTs) that modulate an overactive immune response, such as antibodies against interferon, interleukin, or related T cell targets.…”

Section: Introductionmentioning

confidence: 99%

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Moos

Faller

Glavas

et al. 2020

BioResearch Open Access

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In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

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Repurposing multiple sclerosis drugs: a review of studies in neurological and psychiatric conditions

Cited by 9 publications

References 50 publications

Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

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