Timely therapeutic interventions and long-term therapeutic benefits in multiple sclerosis

Spontaneous myelin repair in multiple sclerosis (MS) provides a striking example of the brain's inherent capacity for sustained and stable regenerative tissue repair—but also clearly emphasizes the limitations of this capacity; remyelination ultimately fails widely in many patients, and disability and handicap accumulate. The observation of endogenous partial myelin repair has raised the possibility that therapeutic interventions designed to supplement or promote remyelination might have a useful and significant impact both in the short term, in restoring conduction, and in the long term, in safeguarding axons. Therapeutic remyelination interventions must involve manipulations to either the molecular or the cellular environment within lesions; both depend crucially on a detailed understanding of the biology of the repair process and of those glia implicated in spontaneous repair, or capable of contributing to exogenous repair. Here we explore the biology of myelin repair in MS, examining the glia responsible for successful remyelination, oligodendrocytes and Schwann cells, their ‘target’ cells, neurons and the roles of astrocytes. Options for therapeutic remyelinating strategies are reviewed, including glial cell transplantation and treatment with growth factors or other soluble molecules. Clinical aspects of remyelination therapies are considered—which patients, which lesions, which stage of the disease, and how to monitor an int–ervention—and the remaining obstacles and hazards to these approaches are discussed.

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Oral teriflunomide in the treatment of relapsing forms of multiple sclerosis: clinical evidence and long-term experience

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756285617722500 ◽

2017 ◽

Vol 10 (12) ◽

pp. 381-396 ◽

Cited By ~ 16

Author(s):

Aaron E. Miller

Keyword(s):

Multiple Sclerosis ◽

Randomized Clinical Trials ◽

Therapeutic Interventions ◽

Imaging Data ◽

Level Of Evidence ◽

Once Daily ◽

Brain Volume Loss ◽

Clinical Episode ◽

Phase Ii And Iii

Key objectives in the treatment of multiple sclerosis (MS) include prevention of relapses, a reduction in the accumulation of disability and slowing of the brain volume loss that occurs from the earliest stages of the disease. Teriflunomide, a once-daily, oral immunomodulatory therapy, has demonstrated efficacy across multiple measures of disease activity and worsening in patients with relapsing forms of MS and in those with a first clinical episode suggestive of MS. In this review, the latest evidence relating to the proposed mechanism of action of teriflunomide in MS is explored, including novel insights provided from the recently completed Teri-DYNAMIC study. Key clinical and magnetic resonance imaging data from the completed long-term extensions of the phase II and III (TEMSO, TOWER and TOPIC) studies are highlighted, and the long-term safety profile of teriflunomide, as evidenced by data from these extension studies, is presented. Although randomized clinical trials represent the highest level of evidence to support the use of therapeutic interventions, it is also important to understand the performance of a particular treatment in the real-world setting. In this regard, the results of the recently completed, global, phase IV Teri-PRO study are of particular interest and provide further insights into the benefits of teriflunomide treatment from the patient perspective. Collectively, the data presented in this review demonstrate a favorable benefit–risk profile for teriflunomide, thereby supporting its long-term use for the treatment of patients with relapsing forms of MS.

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Therapeutic Benefits of Short-Arm Human Centrifugation in Multiple Sclerosis–A New Approach

Frontiers in Neurology ◽

10.3389/fneur.2021.746832 ◽

2022 ◽

Vol 12 ◽

Author(s):

Chrysoula Kourtidou-Papadeli ◽

Christos A. Frantzidis ◽

Christos Bakirtzis ◽

Anatoli Petridou ◽

Sotiria Gilou ◽

...

Keyword(s):

Multiple Sclerosis ◽

Training Programme ◽

Progressive Multiple Sclerosis ◽

Artificial Gravity ◽

Muscle Oxygen ◽

Therapeutic Benefits ◽

Before And After ◽

Degree Of Disability ◽

Brain Reorganization

Short-arm human centrifugation (SAHC) is proposed as a robust countermeasure to treat deconditioning and prevent progressive disability in a case of secondary progressive multiple sclerosis. Based on long-term physiological knowledge derived from space medicine and missions, artificial gravity training seems to be a promising physical rehabilitation approach toward the prevention of musculoskeletal decrement due to confinement and inactivity. So, the present study proposes a novel infrastructure based on SAHC to investigate the hypothesis that artificial gravity ameliorates the degree of disability. The patient was submitted to a 4-week training programme including three weekly sessions of 30 min of intermittent centrifugation at 1.5–2 g. During sessions, cardiovascular, muscle oxygen saturation (SmO2) and electroencephalographic (EEG) responses were monitored, whereas neurological and physical performance tests were carried out before and after the intervention. Cardiovascular parameters improved in a way reminiscent of adaptations to aerobic exercise. SmO2 decreased during sessions concomitant with increased g load, and, as training progressed, SmO2 of the suffering limb dropped, both effects suggesting increased oxygen use, similar to that seen during hard exercise. EEG showed increased slow and decreased fast brain waves, with brain reorganization/plasticity evidenced through functional connectivity alterations. Multiple-sclerosis-related disability and balance capacity also improved. Overall, this study provides novel evidence supporting SAHC as a promising therapeutic strategy in multiple sclerosis, based on mechanical loading, thereby setting the basis for future randomized controlled trials.

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