Brain & Development最新文献

{"title":"Japanese guidelines for treatment of pediatric status epilepticus – 2023","authors":"Kenjiro Kikuchi ,&nbsp;Ichiro Kuki ,&nbsp;Masahiro Nishiyama ,&nbsp;Yuki Ueda ,&nbsp;Ryuki Matsuura ,&nbsp;Tadashi Shiohama ,&nbsp;Hiroaki Nagase ,&nbsp;Tomoyuki Akiyama ,&nbsp;Kenji Sugai ,&nbsp;Kitami Hayashi ,&nbsp;Kiyotaka Murakami ,&nbsp;Hitoshi Yamamoto ,&nbsp;Tokiko Fukuda ,&nbsp;Mitsuru Kashiwagi ,&nbsp;Yoshihiro Maegaki","doi":"10.1016/j.braindev.2024.104306","DOIUrl":"10.1016/j.braindev.2024.104306","url":null,"abstract":"<div><div>The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t₁: at which the seizure should be regarded as an “abnormally prolonged seizure”; and t₂: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the “Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023” (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104306"},"PeriodicalIF":1.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in CYFIP2-associated neurodevelopmental disorders: From human genetics to molecular mechanisms and mouse models","authors":"Ruiying Ma ,&nbsp;U Suk Kim ,&nbsp;Yousun Chung ,&nbsp;Hyae Rim Kang ,&nbsp;Yinhua Zhang ,&nbsp;Kihoon Han","doi":"10.1016/j.braindev.2024.104302","DOIUrl":"10.1016/j.braindev.2024.104302","url":null,"abstract":"<div><div>Cytoplasmic FMR1-interacting protein 2 (CYFIP2) is an evolutionarily conserved protein with a critical role in brain development and function. As a key component of the WAVE regulatory complex, CYFIP2 regulates actin cytoskeleton dynamics, essential for maintaining proper neuronal morphology and circuit formation. Recent studies have also shown that CYFIP2 interacts with various RNA-binding proteins, suggesting its involvement in mRNA processing and translation in neurons. Since 2018, <em>de novo CYFIP2</em> variants have been identified in patients with neurodevelopmental disorders, particularly developmental and epileptic encephalopathy and West syndrome, characterized by early-onset intractable seizures, intellectual disability, microcephaly, and developmental delay. This review summarizes these <em>CYFIP2</em> variants and examines their potential impact on the molecular functions of CYFIP2, focusing on its roles in regulating actin dynamics and mRNA processing/translation. Additionally, we review various <em>Cyfip2</em> mouse models, highlighting the insights they offer into CYFIP2 function, dysfunction, and clinical relevance. Finally, we discuss future research directions aimed at better understanding <em>CYFIP2</em>-associated neurodevelopmental disorders and potential therapeutic strategies.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104302"},"PeriodicalIF":1.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, safety, and tolerability of adjunctive perampanel in the treatment of pediatric patients aged 4–18 years with epilepsy: A single-center, retrospective, observational real-world study","authors":"Yijun Weng ,&nbsp;Xin Rao ,&nbsp;Bihong Ma ,&nbsp;Xi Lin","doi":"10.1016/j.braindev.2024.104305","DOIUrl":"10.1016/j.braindev.2024.104305","url":null,"abstract":"<div><h3>Purpose</h3><div>To observe the efficacy, safety, and tolerability of perampanel (PER) as add-on therapy in children aged 4–18 years with epilepsy in a real-world environment.</div></div><div><h3>Methods</h3><div>A single-center, retrospective, observational study was conducted at the First Affiliated Hospital of Fujian Medical University enrolling children with epilepsy aged 4–18 years who received PER as add-on therapy from January 2021 to November 2022 with 12 months of follow-up. Outcomes included 3-, 6- and 12-month retention, seizure freedom, responder rates, and adverse events (AEs) throughout follow-up.</div></div><div><h3>Results</h3><div>Seventy-eight children were included, of whom three were lost to follow-up. The responder rate at follow-up of 12 months was 54.7 %, the seizure-free rate was 32.0 % and the retention rate was 81.3 %. The number of seizures at baseline was a factor influencing the efficacy of the PER. Nine children reported AEs, with dizziness, drowsiness, and irritability being common.</div></div><div><h3>Conclusions</h3><div>PER is safe, effective, and well tolerated for the treatment of children aged 4–18 years with epilepsy in clinical practice and is a potential option for refractory epilepsy. Patients with lower baseline seizure frequencies are more likely to exhibit a favorable response to PER.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104305"},"PeriodicalIF":1.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levetiracetam for pediatric migraine prophylaxis: A narrative review","authors":"Maryam Shahrokhi ,&nbsp;Amir Mohammad Davari Fard Pur ,&nbsp;Negar Shafaei-Bajestani ,&nbsp;Habibeh Mashayekhi-sardoo","doi":"10.1016/j.braindev.2024.104304","DOIUrl":"10.1016/j.braindev.2024.104304","url":null,"abstract":"<div><h3>Background</h3><div>Migraine, a common primary headache disorder, affects children and adolescents under 18, often bilateral and lasting 2–72  hours, affecting 7.7% of them.</div></div><div><h3>Objective</h3><div>Recent studies on migraine prevention and treatment in children and adolescents have explored the potential benefits of levetiracetam, considering its side effects and potential effects on migraines. Hence, we aimed to review the studies that have examined the possible mechanism and beneficial effects of levetiracetam in children's and adolescents' migraine.</div></div><div><h3>Methods</h3><div>A comprehensive search of English and non-English trials evaluating levetiracetam's effectiveness in pediatric migraine treatment using relevant keywords was conducted in scientific databases including PubMed, Web of Science, and the Cochrane Controlled Trials Register in Feb 2024. The studies included non-randomized controlled trials, uncontrolled trials, and retrospectively reviewed medical charts plus randomized controlled trials.</div></div><div><h3>Results</h3><div>Seven studies were included in this review. They revealed that levetiracetam can promisingly complete the resolution of migraines, and decrease the duration, severity, number of migraine episodes, and frequency of migraine in children. In addition, levetiracetam diminished the Pediatric Migraine Disability Assessment Scale score in them.</div></div><div><h3>Conclusion</h3><div>Seven studies suggest levetiracetam, at doses ranging from 20 to 60 mg/kg/day (250–3000 mg/day), can significantly reduce migraine frequency and duration, but larger controlled trials are needed.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104304"},"PeriodicalIF":1.4,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of COVID-19 pandemic on accesses for seizures in the pediatric emergency department","authors":"Alberto M. Cappellari ,&nbsp;Alessandro Salici ,&nbsp;Antonio A. Tirozzi ,&nbsp;Maria T. Molisso ,&nbsp;Gaia Bruschi ,&nbsp;Elisabetta Lo Iudice ,&nbsp;Sarah Palumbo ,&nbsp;Giuseppe Bertolozzi","doi":"10.1016/j.braindev.2024.104303","DOIUrl":"10.1016/j.braindev.2024.104303","url":null,"abstract":"<div><h3>Background</h3><div>Several studies reported a reduced rate of accesses to pediatric emergency department (ED) for seizures during COVID-19 pandemic. The aim of our study is to evaluate the attendance to pediatric ED for seizures, as well as the influence of seizure type and personal history of seizures on the rate of admissions during the pandemic period.</div></div><div><h3>Methods</h3><div>The number and clinical features of patients admitted to the pediatric ED because of seizures were collected at a single hospital in Milan, Italy, between January 2017 and December 2021. The impact of COVID-19 on the rate of admissions was quantified by using the incidence rate ratio (IRR), comparing the pandemic period (March 2020 to December 2021) to the pre-pandemic (January 2017 to February 2020).</div></div><div><h3>Results</h3><div>During the study period, 1091 patients with seizures were evaluated, 776 (71.1 %) before the pandemic and 315 (28.9 %) during the pandemic. Mean age at evaluation was 3.9 years (range: 1 month to 17 years). During the pandemic, we found a 30 % decrease in evaluation rates per month (IRR, 0.70; 95 % CI, 0.58–0.84), as well as an increased rate of unprovoked seizures (44.8 %, vs 26.5 %, <em>p</em> &lt; 0.001) and focal seizures (29.5 % vs 13.1 %, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Our study showed a reduction in the number of emergency evaluations for seizures during the COVID-19 pandemic. The rate of evaluations was influenced by seizure type and previous history of seizures.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104303"},"PeriodicalIF":1.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and management of plexiform neurofibromas in children with neurofibromatosis 1: A Japanese nationwide survey","authors":"Masafumi Sanefuji ,&nbsp;Takuji Nakamura ,&nbsp;Naoya Higuchi ,&nbsp;Hidetaka Niizuma ,&nbsp;Yasuhiro Kawachi ,&nbsp;Tadashi Shiohama ,&nbsp;Yuichi Yoshida ,&nbsp;Akihiko Asahina ,&nbsp;Muneaki Matsuo","doi":"10.1016/j.braindev.2024.10.008","DOIUrl":"10.1016/j.braindev.2024.10.008","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the clinical characteristics and management of plexiform neurofibromas (PNs) in Japanese children with neurofibromatosis 1 (NF1) in the beginning of a new era of treatment with mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor selumetinib.</div></div><div><h3>Study design</h3><div>Primary and secondary surveys were conducted targeting 1612 departments of pediatrics and dermatology in hospitals with ≥300 beds and children's hospitals, which followed up pediatric patients with NF1-associated PN between April 1, 2022, and April 30, 2024, in Japan.</div></div><div><h3>Results</h3><div>The response rates in the primary and secondary surveys were 40.4 % and 33.8 %, respectively, and 49 patients were followed up in 23 departments. Their ages at the time ranged from 3.3 to 18.8 years and the onset of PN was most frequently recognized during the first year of life. PN was most often observed superficially in the face (39 %), neck (27 %), and head (24 %), followed by the buttocks (20 %), back (18 %), and thighs (18 %). In addition, PNs could be identified radiologically in the spinal/paraspinal regions (18 %) and pelvis (16 %), where they were rarely visible on the corresponding body surfaces. Major morbidities were cosmetic disfigurement (78 %), pain (53 %), and dysfunction (61 %). Selumetinib use was frequent (69 %) and significantly associated with pain (<em>chi</em>-square test, <em>p</em> = 0.014) and dysfunction (<em>p</em> = 0.014).</div></div><div><h3>Conclusions</h3><div>This retrospective nationwide study revealed early onset, diverse tumor locations, and varying morbidities in children with NF1-PN, underscoring the need for early evaluation and optimal treatment. A prospective multicenter registry system is warranted to attain better management.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104300"},"PeriodicalIF":1.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanism of LncRNA GAS5 in cognitive dysfunction induced by sevoflurane anesthesia in neonatal rats","authors":"Xi Chen,&nbsp;Yu Zhang,&nbsp;Nan Hu,&nbsp;Qian Pan,&nbsp;Kaiyuan Wang,&nbsp;Yiqing Yin","doi":"10.1016/j.braindev.2024.10.003","DOIUrl":"10.1016/j.braindev.2024.10.003","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Sevoflurane (Sev) exposure may provoke deleterious effects on cognitive function. This study explores the mechanism of long non-coding RNA growth arrest specific transcript 5 (LncRNA GAS5) in Sev-induced cognitive dysfunction in neonatal rats.</div></div><div><h3>Methods</h3><div>Cognitive dysfunction was induced by Sev anesthesia in 7-day-old Sprague-Dawley rats, followed by open field test, novel object recognition, radial arm maze, and Morris water maze to evaluate cognitive function of rats. The subcellular localization of LncRNA GAS5 was detected by nucleocytoplasmic isolation assay, and the binding of miR-137 to LncRNA GAS5 and NKCC1 was detected by RNA pull down and dual-luciferase reporter assay, respectively. Adenovirus-packaged sh-LncRNA GAS5 was injected into the hippocampus of Sev rats. qRT-PCR and Western blot were performed to detect the expressions of LncRNA GAS5, miR-137 and NKCC1 in the hippocampus of rats.</div></div><div><h3>Results</h3><div>Sev anesthesia led to cognitive dysfunction in neonatal rats. LncRNA GAS5 was highly expressed in Sev rats, and inhibition of LncRNA GAS5 alleviated Sev-induced cognitive dysfunction in rats. LncRNA GAS5 targeted miR-137, and miR-137 inhibited NKCC1 expression. Knockdown of miR-137 or overexpression of NKCC1 reversed the effect of LncRNA GAS5 inhibition on cognitive dysfunction in sev rats.</div></div><div><h3>Conclusion</h3><div>LncRNA GAS5 promotes Sev-induced cognitive dysfunction in neonatal rats via the miR-137/NKCC1 axis.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104295"},"PeriodicalIF":1.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between small for gestational age and motor coordination difficulties in children aged 5–6 years: Insights from the Hokkaido Study on Environment and Children's Health","authors":"Maki Tojo ,&nbsp;Hiroyoshi Iwata ,&nbsp;Naomi Tamura ,&nbsp;Takeshi Yamaguchi ,&nbsp;Kenji J. Tsuchiya ,&nbsp;Satoshi Suyama ,&nbsp;Taku Obara ,&nbsp;Akio Nakai ,&nbsp;Toshio Yoshikawa ,&nbsp;Toyoki Yamagata ,&nbsp;Mariko Itoh ,&nbsp;Keiko Yamazaki ,&nbsp;Sumitaka Kobayashi ,&nbsp;Reiko Kishi","doi":"10.1016/j.braindev.2024.10.004","DOIUrl":"10.1016/j.braindev.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Developmental coordination disorder (DCD) presents motor skill delays in early childhood and has been associated with later maladaptation, necessitating early intervention. However, research on the potential risk factors, particularly in preschool-aged children, remains scarce.</div></div><div><h3>Aims</h3><div>We aimed to explore the association between small for gestational age (SGA) and other factors and motor coordination problems in 5–6-year-olds from the Hokkaido Study on Environment and Children's Health Cohort.</div></div><div><h3>Study design</h3><div>Prospective.</div></div><div><h3>Subjects</h3><div>We analyzed data from &gt;3500 participants from the Hokkaido Study, a prospective birth cohort, and assessed children aged 5–6 years.</div></div><div><h3>Outcome measures</h3><div>Participants underwent assessment with the Developmental Coordination Disorder Questionnaire Japanese version (DCDQ-J). We conducted linear regression analyses adjusted for variables such as the child's sex, maternal age, and maternal smoking history during pregnancy, while also examining the independent associations of each risk factor.</div></div><div><h3>Results</h3><div>Among the 3883 children analyzed for SGA, children with SGA exhibited significantly lower DCDQ-J total scores than non-SGA children (mean difference: −2.25, 95 % confidence interval [−4.19, −0.30], <em>p</em> = 0.02). On the subscales, children with SGA demonstrated significantly lower “Control During Movement” scores than non-SGA children (mean difference: −0.96, 95 % confidence interval [−1.78, −0.13], <em>p</em> = 0.02). Furthermore, the child's sex, maternal smoking, maternal age, and preterm birth were independently associated with DCD.</div></div><div><h3>Conclusions</h3><div>SGA was shown to be one of the risk factors for the manifestation of motor coordination difficulties in 5–6-years old children. In combination with other factors, screening for motor coordination difficulties in SGA children will be an important means of initiating appropriate interventions.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104296"},"PeriodicalIF":1.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of viltolarsen treatment in patients with Duchenne muscular dystrophy: A retrospective study with 3-year follow-up","authors":"Michinori Funato ,&nbsp;Reina Iwata ,&nbsp;Toru Ando ,&nbsp;Motohiro Takeuchi ,&nbsp;Yohei Horibe ,&nbsp;Takashi Funato ,&nbsp;Junko Oota ,&nbsp;Ryoya Uno ,&nbsp;Misaki Yumioka ,&nbsp;Emi Kondo ,&nbsp;Miho Katoyama ,&nbsp;Chie Ito ,&nbsp;Yoshiko Kato ,&nbsp;Yuji Yamada ,&nbsp;Toshifumi Kusukawa","doi":"10.1016/j.braindev.2024.10.005","DOIUrl":"10.1016/j.braindev.2024.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder characterized by severe, progressive muscle wasting. Viltolarsen, a formulation consisting of exon 53-skipping antisense oligonucleotides of the dystrophin gene, has been indicated for some patients with DMD. However, reports describing the efficacy and safety of viltolarsen treatment in patients with DMD, particularly those comparing patients receiving viltolarsen with age- and time-period-matched controls, are limited. This study aimed to confirm the safety and efficacy of viltolarsen treatment in patients with DMD.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed real-world data of patients with DMD aged 6–19 years who started viltolarsen treatment between July 2020 and February 2021 and compared them with age- and time-period-matched patients with DMD who did not receive viltolarsen.</div></div><div><h3>Results</h3><div>Five patients received viltolarsen treatment for over 3 years. Three of the four patients who received viltolarsen once weekly maintained motor function, while one ambulatory patient showed remarkably slow motor function decline. Conversely, eight of nine patients who did not receive viltolarsen and one patient who underwent intermittent viltolarsen treatment showed motor function deterioration. Two patients showed significant treatment-related adverse events, namely swelling of the dorsal surface of the right hand due to extravasation of viltolarsen in one patient and axillary lymph node enlargement due to frequent intravenous infusion in another patient. None of the patients discontinued viltolarsen.</div></div><div><h3>Conclusions</h3><div>Viltolarsen was a safe and effective treatment for patients with DMD, and the findings highlighted the importance of once-weekly and uninterrupted viltolarsen treatment. The distinct safety and efficacy of viltolarsen require further investigation using a large number of cases and a long follow-up period.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104297"},"PeriodicalIF":1.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaperone therapy: Stabilization and enhancement of endogenous and exogenous lysosomal enzymes","authors":"Yoshiyuki Suzuki","doi":"10.1016/j.braindev.2024.10.006","DOIUrl":"10.1016/j.braindev.2024.10.006","url":null,"abstract":"<div><div>Chaperone therapy is a new concept of molecular therapeutic approach to protein misfolding diseases, particularly to lysosomal diseases. Initially we started molecular analysis of culture cells, model animals and patients with Fabry disease and G_M1-gangliosidosis. Some mutant enzyme proteins did not express the catalytic activity because of unstable molecular structure in somatic cells. The small molecule compound (chaperone) corrected misfolding of the unstable mutant protein, resulting in restoration of the enzyme activity (chaperone therapy). This pathological molecular event was studied first in endogenous mutant enzymes. Then a similar molecular interaction was found between the chaperone and the exogenous protein supplied for enzyme replacement therapy (ERT) in Pompe disease. This new chaperone-ERT combination therapy will become another useful technology in order to expand the application of chaperone therapy to a wide range of lysosomal diseases. Thus, chaperone therapy is expected in future for stabilization and enhancement of exogenously supplied ERT enzymes as well as endogenous mutant enzymes.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 1","pages":"Article 104298"},"PeriodicalIF":1.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}