BioDrugs最新文献

{"title":"Eblasakimab, an Anti-IL‑13Rα1 Antibody, Reduces Atopy-Associated Serum Biomarkers in Moderate‑to‑Severe Atopic Dermatitis.","authors":"Ferda Cevikbas, Alison Ward, Karen A Veverka","doi":"10.1007/s40259-024-00685-y","DOIUrl":"10.1007/s40259-024-00685-y","url":null,"abstract":"<p><strong>Introduction: </strong>Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD.</p><p><strong>Methods: </strong>A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600 mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed.</p><p><strong>Results: </strong>Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p = 0.004) and 62.9% (p = 0.003), respectively, for TARC, 35.1% (p = 0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4-6 weeks following the last administered dose.</p><p><strong>Conclusion: </strong>The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor.</p><p><strong>Trial registration number: </strong>NCT04090229.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"821-830"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse Impacts of PEGylated Protein Therapeutics: A Targeted Literature Review.","authors":"Chae Sung Lee, Yogesh Kulkarni, Vicki Pierre, Manish Maski, Christoph Wanner","doi":"10.1007/s40259-024-00684-z","DOIUrl":"10.1007/s40259-024-00684-z","url":null,"abstract":"<p><p>The beneficial effects of polyethylene glycol (PEG)-conjugated therapeutics, such as increased half-life, solubility, stability, and decreased immunogenicity, have been well described. There have been concerns, however, about adverse outcomes with their use, but understanding of those adverse outcomes is still relatively limited. The present study aimed to characterize adverse outcomes associated with PEGylation of protein-based therapeutics on immunogenicity, pharmacologic properties, and safety. A targeted review of English language articles published from 1990 to September 29, 2023, was conducted. Of the 29 studies included in this review, 18 reported adverse safety outcomes such as hematologic complications, hepatic toxicity, injection site reactions, arthralgia, nausea, infections, grade 3 or 4 adverse events (AEs), and AE-related discontinuations and dose modifications. Fifteen studies reported immunogenicity-related outcomes, such as the prevalence of pre-existing antibodies to PEG, treatment-emergent antibody response, and hypersensitivity reactions to PEGylated drugs. Seven studies reported pharmacological outcomes such as increased clearance and reduced activity in response to PEGylated drugs. This review aims to contribute to a balanced view of PEGylated therapies by summarizing the adverse outcomes or lack of benefit associated with PEGylated therapeutics reported in the literature. We identified several studies characterizing adverse outcomes, pharmacological effects, and immunogenicity associated with the use of PEGylated therapeutics. Our findings suggest that using PEGylated therapeutics may require careful monitoring for adverse safety outcomes, including screening and monitoring for pre-existing antibodies and those induced in response to PEGylated therapy, as well as monitoring and adjusting the dosing of PEGylated therapeutics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"795-819"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Satisfaction and Experience with CT-P17 Following Transition from Reference Adalimumab or Another Adalimumab Biosimilar: Results from the Real-World YU-MATTER Study.","authors":"Guillaume Bouguen, Laure Gossec, Vered Abitbol, Eric Senbel, Guillaume Bonnaud, Xavier Roblin, Yoram Bouhnik, Stéphane Nancey, Nicolas Mathieu, Jérôme Filippi, Lucine Vuitton, Stéphane Nahon, Azeddine Dellal, Alice Denis, Lucile Foulley, Caroline Habauzit, Salim Benkhalifa, Hubert Marotte","doi":"10.1007/s40259-024-00681-2","DOIUrl":"10.1007/s40259-024-00681-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biosimilars are cost-effective alternatives to reference products for patients with inflammatory bowel diseases (IBD) and chronic inflammatory rheumatic diseases (CIRD), but patient beliefs can affect adherence to the transition. This study aimed to explore patient experience and satisfaction after switching to CT-P17, a high-concentration (100 mg/mL), citrate-free adalimumab biosimilar.</p><p><strong>Patients and methods: </strong>This observational, multicenter, prospective French study included adult patients with IBD or CIRD who switched to CT-P17 from reference adalimumab (R-ADA; 100 mg/mL) or a low-concentration adalimumab biosimilar (ADA-BioS; 50 mg/mL). Patients completed online questionnaires to assess treatment perceptions, satisfaction, and tolerance at study inclusion (under previous treatment) and over 3 months of CT-P17 treatment. The primary criterion was overall patient satisfaction, which was assessed with the question, \"What is your global satisfaction with the CT-P17 injection?\", using a 7-point Likert scale. Multivariate logistic regression analysis was performed to identify factors associated with increased treatment satisfaction after switching to CT-P17.</p><p><strong>Results: </strong>The total analysis population included 232 patients (IBD 72.0%, CIRD 28.0%). Median patient age was 57.0 years (interquartile range [IQR] 46.0-63.0), 50.4% were men, and median disease duration was 9 years (IQR 5-16). Approximately half of the cohort (51.2%) switched to CT-P17 from an ADA-BioS (including 19.4% from an ADA-BioS with citrate) and half (48.7%) from R-ADA. The proportion of patients who were satisfied with treatment was stable between baseline (under previous treatment) and 3 months (under CT-P17). More patients reported increased satisfaction after switching to CT-P17 from an ADA-BioS (22.7% vs 8.0% when switching from R-ADA; p = 0.002), or from an ADA-BioS containing citrate (28.9% vs 12.3% when switching from a citrate-free ADA-BioS; p = 0.008). Independent prognostic factors for increased satisfaction were previous treatment with an ADA-BioS (odds ratio [OR] 2.88 [95% confidence interval 1.17-7.08]; p = 0.021) and pain at the injection site under previous treatment (OR 1.26 [1.08-1.47]; p = 0.004). Significantly fewer patients reported pain, redness, itching, and hematoma after 3 months of CT-P17 treatment versus baseline (p < 0.001).</p><p><strong>Conclusions: </strong>The majority of patients had stable or increased treatment satisfaction after switching from R-ADA or an ADA-BioS to CT-P17. In particular, switching to CT-P17 from a low-concentration ADA-BioS or an ADA-BioS containing citrate was associated with increased patient satisfaction. An improvement in overall tolerance with CT-P17 versus previous adalimumab treatment was also reported.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT05427942, registered June 22, 2022.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"867-878"},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Arterial Hypertension and TGF-β Superfamily Signaling: Focus on Sotatercept","authors":"Benjamin Stump, Aaron B. Waxman","doi":"10.1007/s40259-024-00680-3","DOIUrl":"https://doi.org/10.1007/s40259-024-00680-3","url":null,"abstract":"<p>Pulmonary arterial hypertension (PAH) is a rare and progressive disease that continues to remain highly morbid despite multiple advances in medical therapies. There remains a persistent and desperate need to identify novel methods of treating and, ideally, reversing the pathologic vasculopathy that results in PAH development and progression. Sotatercept is a first-in-class fusion protein that is believed to primarily inhibit activin signaling resulting in decreased cell proliferation and differentiation, though the exact mechanism remains uncertain. Here, we review the currently available PAH therapies, data highlighting the importance of transforming growth factor-β (TGF-β) superfamily signaling in the development of PAH, and the published and on-going clinical trials evaluating sotatercept in the treatment of PAH. We will also discuss preclinical data supporting the potential use of the fusion protein KER-012 in the inhibition of aberrant TGF-β superfamily signaling to ameliorate the obstructive vasculopathy of PAH.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"27 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure","authors":"Whitney C. Weber, Daniel N. Streblow, Lark L. Coffey","doi":"10.1007/s40259-024-00677-y","DOIUrl":"https://doi.org/10.1007/s40259-024-00677-y","url":null,"abstract":"<p>Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease. Chikungunya virus is endemic in 110 countries and the World Health Organization estimates that it has caused more than 2 million cases of crippling acute and chronic arthritis globally since it re-emerged in 2005. Chikungunya virus outbreaks have occurred in Africa, Asia, Indian Ocean islands, South Pacific islands, Europe, and the Americas. Until recently, no specific countermeasures to prevent or treat chikungunya disease were available. To address this need, multiple vaccines are in human trials. These vaccines use messenger RNA-lipid nanoparticles, inactivated virus, and viral vector approaches, with a live-attenuated vaccine VLA1553 and a virus-like particle PXVX0317 in phase III testing. In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ. In June 2024, Health Canada approved IXCHIQ, and in July 2024, IXCHIQ was approved by the European Commission. On August 13, 2024, the US FDA granted priority review for PXVX0317. The European Medicine Agency is considering accelerated assessment review of PXVX0317, with potential for approval by both agencies in 2025. In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines. We also discuss unanswered questions including potential impacts of pre-existing chikungunya virus immunity on vaccine safety and immunogenicity, whether long-term immunity can be achieved, safety in children, pregnant, and immunocompromised individuals, and vaccine efficacy in people with previous exposure to other emerging alphaviruses in addition to chikungunya virus.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"30 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.","authors":"Yan Zhao, Jing-Yi Li, Bin Yang, Yang-Feng Ding, Li-Ming Wu, Li-Tao Zhang, Jin-Yan Wang, Qian-Jin Lu, Chun-Lei Zhang, Fu-Ren Zhang, Xiao-Hong Zhu, Yu-Mei Li, Xiao-Hua Tao, Qing-Chun Diao, Lin-Feng Li, Jian-Yun Lu, Xiao-Yong Man, Fu-Qiu Li, Xiu-Juan Xia, Jiao-Ran Song, Ying-Min Jia, Li-Bo Zhang, Bo Chen, Jian-Zhong Zhang","doi":"10.1007/s40259-024-00668-z","DOIUrl":"10.1007/s40259-024-00668-z","url":null,"abstract":"<p><strong>Background: </strong>Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials.</p><p><strong>Objective: </strong>We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis.</p><p><strong>Methods: </strong>Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale.</p><p><strong>Results: </strong>In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events.</p><p><strong>Conclusions: </strong>Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"681-689"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospects of Synergy: Local Interventions and CAR T Cell Therapy in Solid Tumors.","authors":"Anne Holtermann, Mila Gislon, Martin Angele, Marion Subklewe, Michael von Bergwelt-Baildon, Kirsten Lauber, Sebastian Kobold","doi":"10.1007/s40259-024-00669-y","DOIUrl":"10.1007/s40259-024-00669-y","url":null,"abstract":"<p><p>Chimeric antigen receptor T cell therapy has been established in the treatment of various B cell malignancies. However, translating this therapeutic effect to treat solid tumors has been challenging because of their inter-tumoral as well as intratumoral heterogeneity and immunosuppressive microenvironment. Local interventions, such as surgery, radiotherapy, local ablation, and locoregional drug delivery, can enhance chimeric antigen receptor T cell therapy in solid tumors by improving tumor infiltration and reducing systemic toxicities. Additionally, ablation and radiotherapy have proven to (re-)activate systemic immune responses via abscopal effects and reprogram the tumor microenvironment on a physical, cellular, and chemical level. This review highlights the potential synergy of the combined approaches to overcome barriers of chimeric antigen receptor T cell therapy and summarizes recent studies that may pave the way for new treatment regimens.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"611-637"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Targets Should Influence Choice of Infliximab Dose Intensification Strategy in Inflammatory Bowel Disease: A Pharmacokinetic Simulation Study.","authors":"Ashish Srinivasan, Daniel van Langenberg, Peter De Cruz, Jonathan Segal, Abhinav Vasudevan, Richard N Upton","doi":"10.1007/s40259-024-00673-2","DOIUrl":"10.1007/s40259-024-00673-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The optimal infliximab dose intensification strategy to address loss of response associated with subtherapeutic infliximab trough levels remains uncertain, as does whether post-intensification trough and treatment targets should influence this decision.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This pharmacokinetic simulation study aimed to identify infliximab dose intensification strategies capable of achieving post-intensification infliximab trough thresholds associated with clinical and objective treatment targets in Crohn's disease and ulcerative colitis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A validated pharmacokinetic infliximab model, applied to 200 simulated patients, identified those with subtherapeutic (&lt; 3.00 mg/L) trough levels after 30 weeks of standard (5 mg/kg 8-weekly) dosing, and subsequently applied 10 dose intensification strategies over a further 32 weeks. The proportion of simulations achieving 32-week post-intensification infliximab trough levels associated with endoscopic remission (ulcerative colitis &gt; 7.50 mg/L, Crohn's disease &gt; 9.70 mg/L) was the primary outcome, with perianal fistula healing (Crohn's disease &gt; 10.10 mg/L) and clinical improvement (ulcerative colitis &gt; 3.70 mg/L, Crohn's disease &gt; 7.00mg/L) evaluated as secondary outcomes. All outcomes were stratified by intensity of dose intensification, with standard (≤ 10 mg/kg 8-weekly or 5 mg/kg 4-weekly; n = 5) and intensive (&gt; 10 mg/kg 8-weekly or 5 mg/kg 4-weekly; n = 5) dosing strategies defined, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The median pre-intensification infliximab trough level was 0.91 mg/L (interquartile range 1.37). Intensive dosing strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (ulcerative colitis 36.48% vs. 10.80%, Crohn's disease 25.98 vs. 4.68%), perianal fistula healing (24.52% vs. 4.36%) and clinical improvement (ulcerative colitis 61.90% vs. 34.86%, Crohn's disease 40.32 vs. 12.08%) than standard intensification strategies (all p &lt; 0.01). When controlling for cumulative (mg/kg) infliximab dose over 32 weeks, strategies that concurrently dose increased and interval shortened achieved the highest infliximab trough levels (all p &lt; 0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This simulation-based analysis highlights the potential of using post-intensification infliximab trough thresholds associated with aspirational treatment targets in Crohn's disease and ulcerative colitis to guide choice of infliximab dose intensification strategy. Intensive dose intensification strategies, particularly those that concurrently dose increase and interval shorten, appear to achieve higher infliximab levels than standard dose intensification strategies. This may be particularly important in the pursuit of stringent endpoints, such as endoscopic remission and fistula healing, which have been consistently associated with higher infliximab trough levels. These findings require va","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"691-702"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Neurological Aspects of Mucopolysaccharidosis Type II: Enzyme Replacement Therapy and Beyond.","authors":"Alessandra Zanetti, Rosella Tomanin","doi":"10.1007/s40259-024-00675-0","DOIUrl":"10.1007/s40259-024-00675-0","url":null,"abstract":"<p><p>Mucopolysaccharidosis type II (MPS II) is a rare, pediatric, neurometabolic disorder due to the lack of activity of the lysosomal hydrolase iduronate 2-sulfatase (IDS), normally degrading heparan sulfate and dermatan sulfate within cell lysosomes. The deficit of activity is caused by mutations affecting the IDS gene, leading to the pathological accumulation of both glycosaminoglycans in the lysosomal compartment and in the extracellular matrix of most body districts. Although a continuum of clinical phenotypes is described, two main forms are commonly recognized-attenuated and severe-the latter being characterized by an earlier and faster clinical progression and by a progressive impairment of central nervous system (CNS) functions. However, attenuated forms have also been recently described as presenting some neurological involvement, although less deep, such as deficits of attention and hearing loss. The main treatment for the disease is represented by enzyme replacement therapy (ERT), applied in several countries since 2006, which, albeit showing partial efficacy on some peripheral organs, exhibited a very poor efficacy on bones and heart, and a total inefficacy on CNS impairment, due to the inability of the recombinant enzyme to cross the blood-brain barrier (BBB). Together with ERT, whose design enhancements, performed in the last few years, allowed a possible brain penetration of the drug through the BBB, other therapeutic approaches aimed at targeting CNS involvement in MPS II were proposed and evaluated in the last decades, such as intrathecal ERT, intracerebroventricular ERT, ex vivo gene therapy, or adeno-associated viral vector (AAV) gene therapy. The aim of this review is to summarize the main clinical aspects of MPS II in addition to current therapeutic options, with particular emphasis on the neurological ones and on the main CNS-targeted therapeutic approaches explored through the years.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"639-655"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Demonstration of Physicochemical and Functional Similarity of the Biosimilar BAT1806/BIIB800 to Reference Tocilizumab.","authors":"Yujie Liu, Jianhua Xie, Zhuxiang Li, Xiong Mei, Di Cao, Shengfeng Li, Linda Engle, Suli Liu, Hans C Ebbers, Cuihua Liu","doi":"10.1007/s40259-024-00672-3","DOIUrl":"10.1007/s40259-024-00672-3","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"725"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}