Degenerative neurological and neuromuscular disease最新文献

{"title":"Childhood Cerebral Adrenoleukodystrophy: Case Report and Literature Review Advocating for Newborn Screening.","authors":"Hamrish Kumar Rajakumar, Varsha Coimbatore Sathyabal, Revathi Nachiappan, Sivakumar Krishnaswamy Vijayaramanujam","doi":"10.2147/DNND.S442985","DOIUrl":"10.2147/DNND.S442985","url":null,"abstract":"<p><strong>Background: </strong>X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India.</p><p><strong>Case presentation: </strong>We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD.</p><p><strong>Conclusion: </strong>ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"14 ","pages":"75-83"},"PeriodicalIF":2.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Pharmacotherapeutic Targets in Alzheimer's Disease and Its Management Using Traditional Medicinal Plants.","authors":"Prabhash Nath Tripathi, Ankit Lodhi, Sachchida Nand Rai, Nilay Kumar Nandi, Shweta Dumoga, Pooja Yadav, Amit Kumar Tiwari, Santosh Kumar Singh, Abdel-Nasser A El-Shorbagi, Sachin Chaudhary","doi":"10.2147/DNND.S452009","DOIUrl":"10.2147/DNND.S452009","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as <i>Ginkgo biloba, Huperzia serrata, Curcuma longa</i> (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. <i>Ginkgo biloba</i>, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. <i>Huperzia serrata</i>, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. <i>Curcuma longa</i>, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"14 ","pages":"47-74"},"PeriodicalIF":0.0,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11114142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient Neonatal Myasthenia Gravis Born to a Mother with Asymptomatic MG: A Case Report.","authors":"Jinrong Yang, Liping Pan, Yaping Liu, Yanrong Wang","doi":"10.2147/DNND.S451611","DOIUrl":"10.2147/DNND.S451611","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"14 ","pages":"15-19"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Perspectives: Obesity and Neurodegeneration - Links and Risks.","authors":"Paul J Kueck, Jill K Morris, John A Stanford","doi":"10.2147/DNND.S388579","DOIUrl":"10.2147/DNND.S388579","url":null,"abstract":"<p><p>Obesity is increasing in prevalence across all age groups. Long-term obesity can lead to the development of metabolic and cardiovascular diseases through its effects on adipose, skeletal muscle, and liver tissue. Pathological mechanisms associated with obesity include immune response and inflammation as well as oxidative stress and consequent endothelial and mitochondrial dysfunction. Recent evidence links obesity to diminished brain health and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD are associated with insulin resistance, an underlying syndrome of obesity. Despite these links, causative mechanism(s) resulting in neurodegenerative disease remain unclear. This review discusses relationships between obesity, AD, and PD, including clinical and preclinical findings. The review then briefly explores nonpharmacological directions for intervention.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"13 ","pages":"111-129"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10774290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Risk Prediction Model to Estimate the Risk of Stroke Among Hypertensive Patients in University of Gondar Comprehensive Specialized Hospital, Gondar, 2012 to 2022.","authors":"Yazachew Moges Chekol, Mehari Woldemariam Merid, Getayeneh Antehunegn Tesema, Tigabu Kidie Tesfie, Tsion Mulat Tebeje, Negalegn Byadgie Gelaw, Nebiyu Bekele Gebi, Wullo Sisay Seretew","doi":"10.2147/DNND.S435806","DOIUrl":"10.2147/DNND.S435806","url":null,"abstract":"<p><strong>Background: </strong>A risk prediction model to predict the risk of stroke has been developed for hypertensive patients. However, the discriminating power is poor, and the predictors are not easily accessible in low-income countries. Therefore, developing a validated risk prediction model to estimate the risk of stroke could help physicians to choose optimal treatment and precisely estimate the risk of stroke.</p><p><strong>Objective: </strong>This study aims to develop and validate a risk prediction model to estimate the risk of stroke among hypertensive patients at the University of Gondar Comprehensive Specialized Hospital.</p><p><strong>Methods: </strong>A retrospective follow-up study was conducted among 743 hypertensive patients between September 01/2012 and January 31/2022. The participants were selected using a simple random sampling technique. Model performance was evaluated using discrimination, calibration, and Brier scores. Internal validity and clinical utility were evaluated using bootstrapping and a decision curve analysis.</p><p><strong>Results: </strong>Incidence of stroke was 31.4 per 1000 person-years (95% CI: 26.0, 37.7). Combinations of six predictors were selected for model development (sex, residence, baseline diastolic blood pressure, comorbidity, diabetes, and uncontrolled hypertension). In multivariable logistic regression, the discriminatory power of the model was 0.973 (95% CI: 0.959, 0.987). Calibration plot illustrated an overlap between the probabilities of the predicted and actual observed risks after 10,000 times bootstrap re-sampling, with a sensitivity of 92.79%, specificity 93.51%, and accuracy of 93.41%. The decision curve analysis demonstrated that the net benefit of the model was better than other intervention strategies, starting from the initial point.</p><p><strong>Conclusion: </strong>An internally validated, accurate prediction model was developed and visualized in a nomogram. The model is then changed to an offline mobile web-based application to facilitate clinical applicability. The authors recommend that other researchers eternally validate the model.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"13 ","pages":"89-110"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10728309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Guidance on the Use of Cladribine Tablets in the Management or Relapsing Multiple Sclerosis: Expert Opinion from Qatar.","authors":"Dirk Deleu, Beatriz Garcia Canibano, Osama Elalamy, Mohamed Sayed Abdelmoneim, Amir Boshra","doi":"10.2147/DNND.S433459","DOIUrl":"https://doi.org/10.2147/DNND.S433459","url":null,"abstract":"<p><p>The increasing availability of high-efficacy disease-modifying therapies (DMT) for the management of relapsing multiple sclerosis (RMS) has increased the potential for individualised patient management but has added complexity to the design of treatment regimens. The long-term application of immune reconstitution therapy (IRT) is supported by an increasing database of real world studies that have added important information on the long-term safety and efficacy of this approach. Cladribine tablets (CladT) is an IRT given as two annual short courses of treatment, following which a majority of patients then demonstrate no significant MS disease activity over a period of years. Whether, and how, to treat patients beyond the first two years of treatment remains a matter for debate, as clinical evidence accumulates. We, a group of neurologists who manage people with RMS in Qatar, provide our expert consensus recommendations on the application and long-term management of CladT therapy based on our experience with treatment in the last 5 years. These include pragmatic recommendations for people with MS disease activity in years 3 and 4 (ie up to four years following first dose of CladT), and for people with or without MS disease activity in subsequent years. We believe our recommendations will help to ensure the optimal application of CladT-based IRT, with the potential benefit for the patient of achieving prolonged periods free of both MS disease symptoms and the burden of regular applications of immunosuppressive DMT.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"13 ","pages":"81-88"},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.","authors":"Jing Ma,&nbsp;Yi-Hui Hou,&nbsp;Zhe-Yan Liao,&nbsp;Zheng Ma,&nbsp;Xiao-Xuan Zhang,&nbsp;Jian-Li Wang,&nbsp;Yun-Bo Zhu,&nbsp;Hai-Lei Shan,&nbsp;Ping-Yue Wang,&nbsp;Cheng-Bo Li,&nbsp;Ying-Lei Lv,&nbsp;Yi-Lan Wei,&nbsp;Jie-Zhi Dou","doi":"10.2147/DNND.S427781","DOIUrl":"10.2147/DNND.S427781","url":null,"abstract":"<p><strong>Background: </strong>Microglia are closely linked to Alzheimer's disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice.</p><p><strong>Objective: </strong>In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia.</p><p><strong>Methods: </strong>We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice.</p><p><strong>Results: </strong>In all leptin treatment group, the brain Aβ levels were decrease. We found increased levels of IL-1β, IL-6 and microglial activation in the hippocampus of adult mice. Using aged mice as an experimental model for chronic neuroinflammation and leptin resistance, the number of Iba-1+ microglia and the levels of IL-1β/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference.</p><p><strong>Conclusion: </strong>Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"13 ","pages":"69-79"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventions to Improve Quality of Life in Multiple Sclerosis: New Opportunities and Key Talking Points.","authors":"Erin Faraclas","doi":"10.2147/DNND.S395733","DOIUrl":"10.2147/DNND.S395733","url":null,"abstract":"<p><strong>Background: </strong>Today, living well with multiple sclerosis (MS) is often measured by a person's overall quality of life rather than being limited to the more traditional metrics of reduced frequency of relapses or progression of disability. This change in focus, to a more holistic view of health, such as overall quality of life, has shifted the views of what both providers and people with multiple sclerosis view as essential for living well with MS.</p><p><strong>Purpose: </strong>This narrative review aims to examine the relevant literature on existing and emerging non-pharmacological interventions shown to improve the quality of life for people with multiple sclerosis across all health domains.</p><p><strong>Methods: </strong>A literature search was conducted on MEDLINE, CINAHL, and Scopus electronic databases using the following search terms: quality of life, health-related quality of life, life quality, life satisfaction, non-pharmacological intervention, non-drug, and intervention. After screening the abstracts, 24 were selected for this review.</p><p><strong>Results: </strong>Common non-pharmacological interventions were used for fatigue and sleep, mental and emotional health, cognition, physical health, and chronic pain. Several non-pharmacological interventions included in this review positively improved the overall quality of life for people with multiple sclerosis. These interventions included exercise, cognitive behavior therapy, and cognitive rehabilitation.</p><p><strong>Conclusion: </strong>Non-pharmacological interventions such as exercise and cognitive behavioral therapy improve the quality of life for people with MS. These interventions should be prescribed more during routine medical care. Translating this research into standard clinical practice should be one area of focus. In addition, higher quality studies, such as randomized control trials, need to be conducted on emerging nonpharmacological interventions to assess effectiveness.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"13 ","pages":"55-68"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/ce/dnnd-13-55.PMC10517677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Respiratory Muscle Training on Respiratory Muscle Strength, Pulmonary Function, and Respiratory Complications in Stroke Survivors: A Systematic Review of Randomized Controlled Trials","authors":"Sisay Deme, Dheeraj Lamba, Abayneh Alamer, Haimanot Melese, Sileshi Ayhualem, Dechassa Imeru, Tsegereda Abebe","doi":"10.2147/DNND.S348736","DOIUrl":"https://doi.org/10.2147/DNND.S348736","url":null,"abstract":"Background Stroke is the most common leading cause of mortality and related morbidities worldwide. After stroke, the motor function of extremities and spinal muscles is significantly impairment, but not only this, it also has attributable factors leading to respiratory dysfunction. Nevertheless, to the extent of the authors’ knowledge, there is a dearth of conclusive studies which examined the effectiveness of RMT on muscle strength, pulmonary function, and respiratory complications of individuals after stroke. Objective The purpose of this systematic review was to evaluate the effectiveness of respiratory muscle training on respiratory muscle strength, pulmonary function, and respiratory complications in patients after stroke. Methods An electronic database search of HINARI, PEDro, PubMed, Cochrane Library and Google scholar was used to identify randomized controlled trials that evaluated the effectiveness of respiratory muscle training in patients with stroke. Articles published from 2010 to 2019 were included. The quality of the articles was assessed using PEDro scale. Articles with abstract only, PEDro scores less than 5, published in non-English language, not freely available articles, and quasi experimental studies were excluded from this study. Results The literature search yielded a total of 7 articles (6 randomized controlled trials with 1 pilot randomized controlled trial) which met inclusion criteria despite their heterogeneity. The methodological quality of all studies ranged from 6 to 8 in Pedro score. Most of the articles reported a significant increase in respiratory muscle strength, respiratory muscle function, and reduced risk of complications with a p value <0.05. Conclusion Respiratory muscle training could potentially improve muscle strength and pulmonary functions of subjects after stroke. Thus, it may reduce stroke-related respiratory complications in subjects after stroke. However, further study is warranted with high quality RCTs and pooled synthesis of results.","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"12 1","pages":"75 - 84"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49304588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ponesimod in the Treatment of Relapsing Forms of Multiple Sclerosis: An Update on the Emerging Clinical Data.","authors":"Serena Ruggieri, Maria Esmeralda Quartuccio, Luca Prosperini","doi":"10.2147/DNND.S313825","DOIUrl":"10.2147/DNND.S313825","url":null,"abstract":"<p><p>Sphingosine 1-phosphate (S1P) receptors are bioactive lipid metabolites that bind five different types of receptors expressed ubiquitously in human body and mediate a broad range of biological functions. Targeting S1P receptors is nowadays a well-established pharmacological strategy to treat multiple sclerosis (MS). However, the adverse events associated with the ancestor (fingolimod), especially in terms of heart conduction and slow reversibility of its pharmacodynamics effect on lymphocytes, have stimulated a search for a S1P modulator with greater selectivity for S1P₁ (the most important immune mechanism to prevent MS-related neuroinflammation). Ponesimod is a second-generation, orally active, directly bioavailable, highly selective, and rapidly reversible modulator of the S1P₁ receptor. Gradual 14-day up-titration of ponesimod mitigates its first-dose effects on heart rate and facilitates its use over fingolimod, as it does not require first-dose cardiac monitoring. Ponesimod is rapidly eliminated within 1 week of discontinuation, thereby representing a more manageable approach in case of vaccination, pregnancy, or adverse events. However, the fast reversibility of ponesimod may also raise concerns about the possibility of a rapid reactivation of disease activity following its discontinuation. Ponesimod was recently approved for the treatment of relapsing MS forms on the basis of a Phase III, double-blind, double-dummy, randomized clinical trial (OPTIMUM) that demonstrated the superiority of ponesimod over teriflunomide on disease activity markers, without unexpected safety concerns. This review summarizes the pharmacodynamic and pharmacokinetic characteristics of ponesimod, and the main Phase II and III studies that led to its approval. Comparisons of ponesimod with other S1P receptor modulators currently available for MS (fingolimod, ozanimod, siponimod) are also provided.</p>","PeriodicalId":93972,"journal":{"name":"Degenerative neurological and neuromuscular disease","volume":"12 1","pages":"61-73"},"PeriodicalIF":2.1,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48099650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}