Fampridine 10mg capsules

Objectives: To compare the effects of various pharmacological treatments on partial test results and adverse effects in patients with cognitive dysfunction (CD) induced by multiple sclerosis (MS) through a network meta-analysis. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were systematically retrieved for randomized controlled trials (RCTs) evaluating the influence of different pharmacological treatments on CD in MS patients. The search was updated until October 8, 2024. The Risk of Bias tool was used to assess the quality of eligible studies, and R was employed for data analysis. Results: Twenrt six studies involving 23,839 MS patients were included for our analysis. Network meta-analysis results indicated that compared to placebo, L-amphetamine may improve memory in MS-induced CD. Memantine may enhance performance on the Paced Auditory Serial Addition Test (PASAT). Compared to memantine, fampridine-SR, ginkgo biloba, and melatonin showed inferior effects. Atomoxetine may improve Symbol Digit Modalities Test (SDMT) scores, outperforming donepezil, ginkgo biloba, L-amphetamine, modafinil, and rivastigmine. Additionally, atomoxetine may improve California Verbal Learning Test (CVLT) performance, compared to ginkgo biloba, L-amphetamine, and memantine. In terms of adverse effects, rivastigmine was less likely to cause dyspepsia. Conclusion: Based on current evidence, L-amphetamine may improve memory in MS-induced CD. Melatonin may enhance PASAT performance, and atomoxetine may improve both SDMT and CVLT scores in these patients. However, rivastigmine was found to have a lower likelihood of causing dyspepsia among the treatments assessed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024623642.

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Background: Slow-release 4-aminopyridine (fampridine) has been shown to improve walking function in people with multiple sclerosis (MS). Its effect on other MS symptoms, such as fatigue, remains controversial. We performed this systematic review to summarize the evidence of the effect of fampridine on fatigue in patients with MS. Methods: PubMed, Scopus, EMBASE, Web of Science, google scholar, and ProQuest were searched for randomized trials or observational studies reporting fatigue scores before and after the treatment with fampridine. We summarized the findings of all relevant reports. Results: A literature search revealed 2,675 records; after removing duplicates, we had 1,504 records. Ninety-seven full texts were evaluated, and finally, 33 studies remained for systematic review. Most studies were done in USA, France, Germany, and Italy. The participants' age and the duration of studies ranged between 39 and 54 years and 2 and 48 weeks, respectively. Out of 20 non-randomized or observational studies, 19 reported a benefit of fampridine in improving MS fatigue; however, only three out of 13 randomized, placebo-controlled studies showed that fampridine improved fatigue better than a placebo. Conclusion: Overwhelmingly positive results of fampridine on fatigue reported in non-randomized and observational studies are compatible with the placebo-responsiveness of fatigue in MS. Randomized, placebo-controlled studies have provided inconsistent results on the effects of fampridine on MS fatigue. Although it is possible that fatigue, at least in a subgroup of people with MS, might respond to fampridine, high-quality, placebo-controlled, blinded, randomized trials are needed to show the efficacy of this medication in improving MS fatigue.

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INTRODUCTION: Remyelination failure hampers symptomatic recovery in multiple sclerosis (MS), underlining the importance of developing remyelinating therapies. Optic neuritis is currently the most established method of measuring remyelination in MS trials. Complementary more generalisable methods of measuring remyelination are required to confirm treatment efficacy. Measuring internuclear ophthalmoplegia (INO) with infrared oculography provides such a method. Moreover, this method can be expanded with a test for selecting likely treatment responders by using fampridine. The aim of this trial is to investigate the (long-term) remyelinating effects of clemastine fumarate in patients with MS and INO and to evaluate if treatment response can be predicted using fampridine. METHODS AND ANALYSIS: RESTORE is a single-centre double-blind randomised placebo-controlled trial of clemastine fumarate versus placebo. Prior to clemastine treatment improvement in oculographic features of INO after a single 10 mg dose of fampridine is measured in all participants and used to predict the treatment response to clemastine. Eighty individuals with MS and INO will be 1:1 randomised to 4 mg of clemastine fumarate two times a day for 6 months or equivalent placebo. Our primary outcome is improvement in the Versional Dysconjugacy Index-area under the curve, measured by infrared oculography after 6 months of treatment. Participants are assessed for persistent treatment effects 6, 18 and 30 months after end of treatment. Secondary outcome measures include other oculography parameters including double-step saccades, retinal imaging, visual acuities, physical disability, cognition and patient-reported outcomes. ETHICS AND DISSEMINATION: Clemastine is a registered and very well-established drug with well-known safety and side effects. The protocol was approved by the medical ethical committee of the Amsterdam UMC, location VUMC and the Dutch Central Committee on Research Involving Human Subject. Written informed consent is obtained from all participants. The results will be published in peer-reviewed medical scientific journals. TRIAL REGISTRATION NUMBER: EudraCT: 2021-003677-66, ClinicalTrials.gov: NCT05338450.

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Abstract Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine’s impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon P = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (r s = −0.37, P = 0.014, n = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, P = 0.027, R 2 β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine’s capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.

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Multiple sclerosis (MS) manifests itself with plaque formation as a result of defensive T and B cells in the immune system perceiving the myelin sheath around nerve cells as a foreign substance to the body and trying to destroy it, for an unknown reason.In short, it is an autoimmune inflammatory demyelinating disease of the central nervous system. In multiple sclerosis, various interventions such as medication, physical therapy, and stem cell therapy are used to improve patients' quality of life. The goal of autologous hematopoietic stem cell transplantation (AHSCT) is to eliminate and replace the patient's pathogenic immune system to achieve long-term remission of MS. Here, we will present our experience with autologous stem cell transplantation performed in our center for an MS case that had previously received both medical and physical therapy and failed to respond. Key words: multiple sclerosis, autologous stem cell transplantation The 41-year-old male patient was diagnosed with MS in 2012 and has been wheelchair-bound for about 3 years. Glatiramer acetate was started at the time of diagnosis. As the patient's complaints increased, fampridine and ocrelizumab treatments were given, respectively. The patient, who did not respond to treatment, was evaluated as having secondary progressive MS and an autologous stem cell transplant was planned. Mobilization was performed with cyclophosphamide + G-CSF in July 2023. In September 2023, AHSCT was performed with cyclophosphamide (40 mg/kg, 2400 mg in total, 5 days), Mesna (40 mg/kg/day, 2400 mg in total, 5 days) and ATG (360 mg in total) protocol. The patient, who had platelet engraftment on day +9 and neutrophil engraftment on day +11 after AHSCT, was discharged with outpatient clinic control. Despite many advances in MS treatment, there is still no definitive treatment answer. Autologous hematopoietic stem cell transplantation may be promising, as observed in several studies. The aim of AHSCT is to eliminate and replace the patient's pathogenic immune system to ensure long-term remission of MS (1). In the MIST study; One group of patients with relapse-refractory MS (RRMS) underwent myeloablative AHSCT with cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG), and the other group was given disease-modifying therapy. During an average follow-up of 2 years, disease progression was 5% in the AHSCT group and 62% in the other group. In addition, those who underwent AHSCT had fewer relapses, and the rate of lesion healing on MRI was observed to be higher in the AHSCT group (2). In the HALT-MS study, event-free survival and improvement in neurological functions were observed at higher rates in patients who underwent AHSCT after high-dose immunotherapy (3-4). In a study conducted in Sweden, no recurrence or progression was observed in the first 3 years of treatment after AHSCT, and it was also stated that no new lesions developed on MRI (5). Although studies show the potential benefits of AHSCT, more long-term data from randomized controlled trials are needed to evaluate the effectiveness and safety of this intervention in the treatment of RRMS.

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Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury-specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research ( in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc (AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide, (-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

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