Degenerative Neurological and Neuromuscular Disease最新文献

{"title":"Istradefylline for OFF Episodes in Parkinson's Disease: A US Perspective of Common Clinical Scenarios.","authors":"Stuart H Isaacson,&nbsp;Sagari Betté,&nbsp;Rajesh Pahwa","doi":"10.2147/DNND.S245197","DOIUrl":"https://doi.org/10.2147/DNND.S245197","url":null,"abstract":"<p><p>The effective management of OFF episodes remains an important unmet need for patients with Parkinson's disease (PD) who develop motor complications with long-term levodopa therapy. Istradefylline is a selective adenosine A_2A receptor antagonist for the treatment of patients with PD experiencing OFF episodes while on levodopa/decarboxylase inhibitor. Originally approved in Japan, istradefylline was recently approved in the USA. In this article, we provide a specific review of the four clinical studies that the FDA included in the approval of istradefylline in the USA, and discuss common clinical scenarios, based on our experience, where treatment with istradefylline may benefit patients experiencing motor fluctuations.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"97-109"},"PeriodicalIF":0.0,"publicationDate":"2022-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/31/dnnd-12-97.PMC9329678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40659153","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":"Mechanisms of Action of <i>Semen Ziziphi spinosae</i> in the Treatment of Tourette Syndrome.","authors":"Fei Fan,&nbsp;Fei Han,&nbsp;Long Hao","doi":"10.2147/DNND.S370278","DOIUrl":"https://doi.org/10.2147/DNND.S370278","url":null,"abstract":"<p><strong>Background: </strong><i>Semen Ziziphi spinosae</i>, known as Suanzaoren (SZR) in Chinese, is a Chinese herbal medicine widely used in sedatives and tranquilizers. Although SZR is important for the clinical treatment of Tourette syndrome (TS), its mechanism of action remains unclear. Therefore, we investigated the pharmacological mechanisms of SZR in TS treatment using network pharmacology and systems biology approaches.</p><p><strong>Methods: </strong>The bioactive components and potential targets of SZR were screened using the TCMSP database. UniProt was used to identify targets by mapping the known genes related to SZR. The known genes related to TS were identified by GeneCards and OMIM databases. A protein-protein interaction network was constructed using information from STRING 11.0 database. Cytoscape 3.8.0 software and Bioinformatics online platform were used for plotting this network. Gene ontology and KEGG enrichment analyses were performed using Metascape. Finally, AutoDock was used to verify the molecular docking.</p><p><strong>Results: </strong>We found that SZR had 10 active compounds. There were 30 overlapping target genes between TS and SZR. These genes were associated with several signaling and metabolic pathways. <i>AChE, SLC6A4</i>, and <i>HTR3A</i> were the top three hub genes. The active components in SZR had a high binding affinity for the key targets.</p><p><strong>Conclusion: </strong>SZR therapy for TS could achieve network regulation through the action of various active components of Chinese medicine on different targets and generate a complex regulatory relationship via interaction with potential targets, thereby playing a therapeutic role. Thus, SZR is a potential candidate for treating TS because it regulates nervous system functions.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"85-96"},"PeriodicalIF":0.0,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/21/dnnd-12-85.PMC9297330.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40536051","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":"Updated Perspectives on the Challenges of Managing Multiple Sclerosis During Pregnancy.","authors":"Ramón Villaverde-González","doi":"10.2147/DNND.S203406","DOIUrl":"https://doi.org/10.2147/DNND.S203406","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, and degenerative disease that is up to three times more frequent in young women. MS does not alter fertility and has no impact on fetal development, the course of pregnancy, or childbirth. The Pregnancy in Multiple Sclerosis Study in 1998 showed that pregnancy, mostly in untreated women, did not adversely affect MS, as disease activity decreased during pregnancy (although it significantly increased in the first trimester postpartum). These findings, together with the limited information available on the potential risks of fetal exposure to disease modifying treatments (DMTs), meant that women were advised to delay the onset of DMTs, stop them prior to conception, or, in case of unplanned pregnancy, discontinue them when pregnancy was confirmed. Now, many women with MS receive DMTs before pregnancy and, despite being considered a period of MS stability, up to 30% of patients could relapse in the first trimester postpartum. Factors associated with an increased risk of relapse and disability during pregnancy and postpartum include relapses before and during pregnancy, a greater disability at the time of conception, the occurrence of relapses after DMT cessation before conception, and the use of high-efficacy DMTs before conception, especially natalizumab or fingolimod. Strategies to prevent postpartum activity are needed in some patients, but consensus is lacking regarding the therapeutic strategies for women with MS of a fertile age. This, along with the increasing number of DMTs, means that the decision-making processes in aspects related to family planning and therapeutic strategies before, during, and after pregnancy are increasingly more complex. The purpose of this review is to provide an update on pregnancy-related issues in women with MS, including recommendations for counseling, general management, use of DMTs in pre-pregnancy, pregnancy, and postpartum periods, and breastfeeding-related aspects of DMTs.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":"12 ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2e/36/dnnd-12-1.PMC8743861.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39678463","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":"The Assessment of Major Histocompatibility Complex (MHC) Class-I Expression in Different Neuromuscular Diseases.","authors":"Maher Kurdi,&nbsp;Aysha Alshareef,&nbsp;Ahmed K Bamaga,&nbsp;Zahir T Fadel,&nbsp;Moafaq S Alrawaili,&nbsp;Sahar Hakamy,&nbsp;Fawaz Mohamed,&nbsp;Ahmad R Abuzinadah,&nbsp;Bassam M J Addas,&nbsp;Nadeem Shafique Butt","doi":"10.2147/DNND.S340117","DOIUrl":"https://doi.org/10.2147/DNND.S340117","url":null,"abstract":"<p><strong>Background: </strong>Major histocompatibility complex (MHC) class-1 antigen is a glycoprotein expressed in all nucleated cells. The aim of this study was to assess MHC class-I expression in different neuromuscular diseases.</p><p><strong>Methods: </strong>The authors reviewed the data of 54 patients with neuromuscular diseases. Anti MHC class-I antibody was performed on the frozen muscle tissues using immunohistochemistry. MHC class-I was scored based on its expression on muscle fibers (0: normal, 1: expression <5 fibers, 2: expression in 5-10 fibers, 3: expression in >10 fibers). The pattern was only assessed in cases with MHC class-I scored 3 as: (1: Sarcocapillary, 2: Sarcocapillary and necrotic fibers, 3: Perifascicular). The relationship between MHC class-I expression and neuromuscular diseases was statistically analyzed.</p><p><strong>Results: </strong>The mean age of the patients was 39.1 ± 18.5 years. Around 50% of patients showed normal CK levels and 5% of the cases showed elevated CK levels. There was a significance difference in MHC class-I expression between cases with normal and elevated CK levels when MHC class-I score was 3 (p= 0.020). There was a significant difference in MHC class-I expression among different neuromuscular diseases (p<0.001). All cases with idiopathic inflammatory myopathies (IIMs) have expressed MHC class-I in more than 10 fibers. MHC class-I was expressed in 15 cases of non-IIMs.</p><p><strong>Conclusion: </strong>MHC class-I cannot be solely used as a biomarker to distinguish IIMs from non-IIMs. The presence of MHC class-I molecules in non-IIMs might be related to immunoproteasomes mechanism. Further studies, with different muscle proteins expression and genomic sequencing, must be conducted to understand the role of MHC Class-I in neuromuscular diseases.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"61-68"},"PeriodicalIF":0.0,"publicationDate":"2021-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/6b/dnnd-11-61.PMC8727622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39799398","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":"Effect of Ankle Joint Mobilization with Movement on Range of Motion, Balance and Gait Function in Chronic Stroke Survivors: Systematic Review of Randomized Controlled Trials.","authors":"Abayneh Alamer,&nbsp;Haimanot Melese,&nbsp;Kefale Getie,&nbsp;Sisay Deme,&nbsp;Molla Tsega,&nbsp;Sileshi Ayhualem,&nbsp;Gebremeskel Birhanie,&nbsp;Yohannes Abich,&nbsp;Asmare Yitayeh Gelaw","doi":"10.2147/DNND.S317865","DOIUrl":"https://doi.org/10.2147/DNND.S317865","url":null,"abstract":"<p><strong>Background: </strong>Ankle joint mobilization with movement has been speculated to be an important intervention for enhancing range of motion, balance, and gait functions in chronic stroke survivors. Nonetheless, there is a scarcity of recent conclusive evidence that evaluates its efficacy in chronic stroke patients. The purpose of this review was to synthesize existing evidence on the efficacy of mobilization with movement therapy on range of motion, balance, and gait performance in subjects after stroke.</p><p><strong>Methods: </strong>A comprehensive systematic search of literature was performed using the following databases: PubMed/Medline, CINAHL, AMED, PEDro, Cochrane Library, and Scopus. Physiotherapy Evidence Database (PEDro) scale was used to evaluate the methodological quality of included trials. The primary outcome measures of this review were dorsiflexion range of motion (DF-ROM), and Berg balance scale (BBS). This review was reported in accordance with PRISMA statement guidelines. Due to variations in relevant trials, meta-analysis was not carried out.</p><p><strong>Results and conclusions: </strong>Seven randomized controlled trials with a total of 224 subjects were analyzed. Evidence of overall quality was graded from moderate to high. This review found that mobilization with movement therapy could be an alternative rehabilitative intervention for subjects with chronic stroke to increase range of motion, balance, and gait ability. However, the evidence remains preliminary due to the small number of participants. Large-scale RCTs in the future are warranted to investigate the efficacy of mobilization with movement in subgroups of chronic stroke subjects.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"51-60"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4a/f3/dnnd-11-51.PMC8420562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39408290","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":"RANTES/CCL5 Signaling from Jawbone Cavitations to Epistemology of Multiple Sclerosis - Research and Case Studies.","authors":"Johann Lechner,&nbsp;Volker von Baehr,&nbsp;Fabian Schick","doi":"10.2147/DNND.S315321","DOIUrl":"10.2147/DNND.S315321","url":null,"abstract":"<p><strong>Background: </strong>The role played by signaling pathways in the cell-cell communication associated with multiple sclerosis (MS) progression has become a critical area in research. Chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted), also named chemokine C-C motif ligand 5 (CCL5; R/C), is a protein that has been investigated in neuroinflammatory research due to its link to MS development.</p><p><strong>Objective: </strong>Research on bone marrow defects in the jawbone (BMDJ), which morphologically presents as fatty-degenerative osteonecrosis of the jawbone (FDOJ), presents overexpression of R/C signaling in affected areas. Here, we try to elucidate the potential link between jawbone-derived R/C and MS.</p><p><strong>Methods: </strong>Seventeen BMDJ/FDOJ samples extracted from 17 MS patients, as well as samples from 19 healthy controls, were analyzed for R/C expression using bead-based Luminex^® analysis. The serum R/C levels from 10 MS patients were examined. Further, bone density, histology, and R/C expression were analyzed in two clinical case studies.</p><p><strong>Results: </strong>High R/C overexpression was found in all BMDJ/FDOJ samples obtained from the MS group. Serum R/C levels were also upregulated in the MS group. R/C serum levels in the MS cohort were higher than in the healthy controls. In contrast, the histology of BMDJ/FDOJ samples showed no inflammatory cells.</p><p><strong>Discussion: </strong>R/C-induced \"silent inflammation\" in MS is widely discussed in the scientific literature, along with R/C triggering of inflammation in the central nervous system, which might be key in the development of MS.</p><p><strong>Conclusion: </strong>The authors suspect that BMDJ/FDOJ may serve as a trigger of MS progression via R/C overexpression. As such, the dental and medical communities should be made aware of BMDJ/FDOJ in cases of MS.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"41-50"},"PeriodicalIF":0.0,"publicationDate":"2021-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/48/dnnd-11-41.PMC8275106.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39186648","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":"Clinical Utility of Opicapone in the Management of Parkinson's Disease: A Short Review on Emerging Data and Place in Therapy.","authors":"Linda Azevedo Kauppila,&nbsp;Daniela Pimenta Silva,&nbsp;Joaquim J Ferreira","doi":"10.2147/DNND.S256722","DOIUrl":"https://doi.org/10.2147/DNND.S256722","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a prevalent neurodegenerative disorder, and levodopa (L-dopa) remains the most efficacious drug treatment for PD and a gold-standard for symptom control. Nonetheless, a significant majority of PD patients develop motor fluctuations over their disease course, with a significant impact on quality-of-life, meaning control of such complications translates into a fundamental clinical need. Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for end-of-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Opicapone (OPC), a once-daily, long-acting COMT-i, is the most recent and potent of its class, having been licensed in Europe in 2016 as an add-on to preparations of L-dopa/DOPA decarboxylase inhibitors in PD patients with EoD motor fluctuations. More recently, it has also received approval in the USA and Japan in 2020. Two high-quality positive efficacy studies (double-blind Phase III clinical trials) established OPC efficacy with significant reduction in OFF time (average 60 minutes vs placebo), without concomitant increase of distressing dyskinesias during ON time. These beneficial effects were sustained in open-label extension studies, without unexpected safety issues or adverse events, with dyskinesia having been the most frequent complaint. OPC also avoids liver toxicity and gastrointestinal issues compared with previous COMT-i. In this review, we aimed to cover OPC's lifecycle (synthesis to commercialization), its clinical pharmacological data, safety, tolerability and pharmacovigilance evidence, and discuss its role in the management of motor fluctuations in PD as well as its emerging place in international recommendations.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/f6/dnnd-11-29.PMC8123942.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38913767","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":"Melatonin Improves Short-Term Spatial Memory in a Mouse Model of Alzheimer's Disease.","authors":"Samah Labban, Fahad S Alshehri, Maher Kurdi, Yasser Alatawi, Badrah S Alghamdi","doi":"10.2147/DNND.S291172","DOIUrl":"10.2147/DNND.S291172","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a neurodegenerative disease that has become a leading cause of death in recent years. Impairments in spatial learning and memory are an important clinical feature of AD. Melatonin (MLT), the main product secreted by the pineal gland, showed multiple antioxidant, anti-inflammatory, and neuroprotective properties.</p><p><strong>Purpose: </strong>The present study aimed to explore the possible prophylactic effects of MLT against spatial memory deficits in a sporadic mouse model of AD induced by D-galactose and aluminium chloride (AlCl₃).</p><p><strong>Methods: </strong>Four groups of mice (<i>n</i> = 10 per group) were prepared: control, AD (the D-galactose and AlCl₃ AD model group), AD+MLT (AD mice treated with 80 mg/kg MLT), and AD+DON (AD mice treated with 3 mg/kg donepezil). We then used the object location and Y-maze tests to assess spatial memory in the four groups. Gene expression levels of brain-derived neurotrophic factor (<i>Bdnf</i>) and cAMP-responsive element-binding protein (<i>Creb1</i>) were measured using real-time polymerase chain reaction.</p><p><strong>Results: </strong>We found that MLT improved spatial memory in the sporadic AD mice. MLT ameliorated <i>Creb1</i> gene expression and significantly increased <i>Bdnf</i> gene expression in the hippocampus of AD model mice compared with the AD group.</p><p><strong>Conclusion: </strong>MLT could have a substantial potential to alleviate memory impairment in sporadic AD if introduced at early stages.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":" ","pages":"15-27"},"PeriodicalIF":0.0,"publicationDate":"2021-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/b3/dnnd-11-15.PMC8110255.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38978713","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":"Bioactive Compounds and Traditional Herbal Medicine: Promising Approaches for the Treatment of Dementia.","authors":"Nafaa Alzobaidi,&nbsp;Huma Quasimi,&nbsp;Nasr A Emad,&nbsp;Abdulsalam Alhalmi,&nbsp;Maaz Naqvi","doi":"10.2147/DNND.S299589","DOIUrl":"https://doi.org/10.2147/DNND.S299589","url":null,"abstract":"<p><p>Dementia is a term that encompasses a group of clinical symptoms affecting memory, thinking and social abilities, characterized by progressive impairment of memory performance and cognitive functions. There are several factors involved in the pathogenesis and progression of dementia, such as old age, brain ischemia, toxin exposure, and oxidative stress. There are extensive similarities between dementia and Alzheimer's disease (AD) either in clinical manifestations or experimental animal models. AD is the most dominant form of dementia, characterized by the accumulation of beta-amyloid protein and cholinergic neurotransmission deficits in the brain. Currently available medications for the treatment of dementia, such as choline esterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists (memantine), have short-term efficacy and only relieve symptoms rather than targeting the main underlying pathogenesis. Several animal studies and clinical trials are being conducted to provide a rational approach to these medicinal plants in the prevention or treatment of memory deficits. This review highlights the potential effects of medicinal plants and their derived lead molecules, and explains the related mechanisms and effects reviewed from published literature as major thrust aspects and hopeful strategies in the prevention or treatment of dementia.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":"11 ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/23/dnnd-11-1.PMC8051957.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641805","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":"Advances in Newborn Screening and Presymptomatic Diagnosis of Spinal Muscular Atrophy.","authors":"Maria Jędrzejowska","doi":"10.2147/DNND.S246907","DOIUrl":"https://doi.org/10.2147/DNND.S246907","url":null,"abstract":"<p><p>Spinal muscular atrophy 5q (SMA5q) is one of the most severe and common genetic diseases. In the natural course, the disease leads to premature death (in acute forms) or severe motor disability (in chronic forms). As the genetic basis of SMA is very homogenous, the diagnostics are based entirely on simple and sensitive genetic testing. In the last few years, innovative methods of therapy have been developed based on <i>SMN2</i> gene modification, such as splicing, or replacement of the damaged <i>SMN1</i> gene (gene therapy). Although these approaches have shown high efficacy, results depend on the age/disease stage at which therapy is initiated. The best results have been obtained in presymptomatic patients. Indeed, introduction of therapy in the pre- or early symptomatic stage of the disease seems to be crucial for maximizing effects. Thus, all the criteria for the implementation of neonatal screening for SMA have been met, and many countries, ie, the USA, Germany, Belgium, and Australia, have started NBS national/pilot programs for SMA. The initial results of these programs indicate a high frequency of the disease, reaching 1 per 7 thousand live births in Europe, as well as early symptomatology (first weeks of life in severe cases) and a high frequency of patients with 4 <i>SMN2</i> copies. Overall, the time for therapy inclusion in patients with 4 <i>SMN2</i> copies remain under discussion. More precise predictors/biomarkers of the clinical course are needed. At the same time, it seems advisable to offer other solutions, such as population carrier screening. As the long-term effects of different treatments on the natural history of SMA are unknown, the natural history of the disease needs to be re-evaluated.</p>","PeriodicalId":11147,"journal":{"name":"Degenerative Neurological and Neuromuscular Disease","volume":"10 ","pages":"39-47"},"PeriodicalIF":0.0,"publicationDate":"2020-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/DNND.S246907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38753380","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}