Science Translational Medicine最新文献

{"title":"The response to anti–PD-1 and anti–LAG-3 checkpoint blockade is associated with regulatory T cell reprogramming","authors":"Annah S. Rolig,&nbsp;Xiyu Peng,&nbsp;Elizabeth R. Sturgill,&nbsp;Nisha Holay,&nbsp;Melissa Kasiewicz,&nbsp;Courtney Mick,&nbsp;Grace Helen Mcgee,&nbsp;William Miller,&nbsp;Yoshinobu Koguchi,&nbsp;Johanna Kaufmann,&nbsp;Niranjan Yanamandra,&nbsp;Sue Griffin,&nbsp;James Smothers,&nbsp;Matthew Adamow,&nbsp;Jasme Lee,&nbsp;Ronglai Shen,&nbsp;Margaret K. Callahan,&nbsp;William L. Redmond","doi":"10.1126/scitranslmed.adk3702","DOIUrl":"10.1126/scitranslmed.adk3702","url":null,"abstract":"<div >Immune checkpoint blockade (ICB) has revolutionized cancer treatment; however, many patients develop therapeutic resistance. We previously identified and validated a pretreatment peripheral blood biomarker, characterized by a high frequency of LAG-3⁺ lymphocytes, that predicts resistance in patients receiving anti–PD-1 (aPD-1) ICB. To better understand the mechanism of aPD-1 resistance, we identified murine tumor models with a high LAG-3⁺ lymphocyte frequency (LAG-3^hi), which were resistant to aPD-1 therapy, and LAG-3^lo murine tumor models that were aPD-1 sensitive, recapitulating the predictive biomarker we previously described in patients. LAG-3^hi tumor-bearing mice were sensitive to aPD-1 + anti–LAG-3 (aLAG-3) therapy, and this benefit was CD8⁺ T cell dependent. The efficacy of combination therapy was enhanced in LAG-3^hi (but not LAG-3^lo) mice with depletion of CD4⁺ T cells. Furthermore, responses to aPD-1 + aLAG-3 correlated with regulatory T cell (T_reg) phenotypic plasticity in LAG-3^hi mice, suggesting a specific role for T_regs in response to aPD-1 + aLAG-3 treatment. Using T_reg fate–tracking <i>Foxp3^GFP-Cre-ERT2</i> × ROSA^YFP reporter mice, we demonstrated that expanded populations of unstable T_regs correlated with improved response to combination therapy in LAG-3^hi mice. Complementing these preclinical data, an increased proportion of unstable T_regs also correlated with higher response rate and improved survival after aPD-1 + aLAG-3 therapy in a cohort of patients with metastatic melanoma (<i>n</i> = 117). These data indicate that T_reg phenotypic plasticity affects aPD-1 + aLAG-3 responsiveness, which may represent a biomarker to aid patient selection and a rational therapeutic target for a subset of PD-1–refractory patients.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 793","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial genomics: Mapping the landscape of fibrosis","authors":"Prasad Palani Velu,&nbsp;Roxanna E. Abhari,&nbsp;Neil C. Henderson","doi":"10.1126/scitranslmed.adm6783","DOIUrl":"10.1126/scitranslmed.adm6783","url":null,"abstract":"<div >Organ fibrosis causes major morbidity and mortality worldwide. Treatments for fibrosis are limited, with organ transplantation being the only cure. Here, we review how various state-of-the-art spatial genomics approaches are being deployed to interrogate fibrosis across multiple organs, providing exciting insights into fibrotic disease pathogenesis. These include the detailed topographical annotation of pathogenic cell populations and states, detection of transcriptomic perturbations in morphologically normal tissue, characterization of fibrotic and homeostatic niches and their cellular constituents, and in situ interrogation of ligand-receptor interactions within these microenvironments. Together, these powerful readouts enable detailed analysis of fibrosis evolution across time and space.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 793","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for the Research Article “A gut Eggerthella lenta–derived metabolite impairs neutrophil function to aggravate bacterial lung infection” by L.-L. Wang et al.","authors":"","doi":"10.1126/scitranslmed.adx6062","DOIUrl":"10.1126/scitranslmed.adx6062","url":null,"abstract":"","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 793","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen V regulates renal function after kidney injury and can be pharmacologically targeted to enhance kidney repair in mice","authors":"Lianjiu Su,&nbsp;Qihao Sun,&nbsp;Yusheng Li,&nbsp;Juan Felipe Alvarez,&nbsp;Bo Tao,&nbsp;Guanglin Zhang,&nbsp;Yiqian Gu,&nbsp;Mark R. Hanudel,&nbsp;Alejandro Espinoza,&nbsp;Linlin Zhang,&nbsp;Calvin Pan,&nbsp;James R. Hilser,&nbsp;Jaana A. Hartiala,&nbsp;Shen Li,&nbsp;Matteo Pellegrini,&nbsp;Hooman Allayee,&nbsp;Aldons J. Lusis,&nbsp;Arjun Deb","doi":"10.1126/scitranslmed.ads7714","DOIUrl":"10.1126/scitranslmed.ads7714","url":null,"abstract":"<div >Kidney fibrosis determines clinical outcomes in individuals with chronic kidney disease (CKD). The stoichiometric ratio of collagens in renal scar differs from that of healthy kidney extracellular matrix (ECM), but the functional importance of altered collagen types in injured kidneys remains unclear. Using human population studies, we show that circulating protein and renal mRNA amounts of collagen V A1 (COL5A1) exhibited associations with kidney disease and incident CKD risk. We show that <i>Col5a1</i> regulates the degree of postinjury fibrosis and renal function. Mice with conditionally knocked out <i>Col5a1</i> (<i>Col5a1</i> CKO) exhibited decreased renal function and greater renal fibrosis after dietary adenine- or ureteric obstruction–mediated kidney injury. Renal fibroblasts in <i>Col5a1</i> CKO animals up-regulated the profibrotic αvβ3 integrin. Inhibition of αvβ3 signaling with a small molecule, cilengitide, rescued postinjury renal function in <i>Col5a1</i> CKO animals. Using the hybrid mouse diversity panel that comprises 100 diverse inbred strains of mice, we observed that gene expression of <i>Col5a1</i> after injury exhibited genetic variation across 100 strains. Strains with low <i>Col5a1</i> expression after injury exhibited worse renal function compared with animals that had higher degrees of expression. We next measured <i>Col5a1</i> expression in peripheral blood mononuclear cells in mice to identify nonresponder strains that did not have increased <i>Col5a1</i> expression after kidney injury. We observed that administration of cilengitide in nonresponder strains significantly rescued postinjury renal fibrosis and function. These studies point to the feasibility of precision medicine approaches to target <i>Col5a1</i> for enhancing renal repair.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 793","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis","authors":"Qi Wang,&nbsp;Taida Huang,&nbsp;Zihan Zheng,&nbsp;Yixun Su,&nbsp;Zhonghao Wu,&nbsp;Cong Zeng,&nbsp;Guangdan Yu,&nbsp;Yang Liu,&nbsp;Xiaorui Wang,&nbsp;Hui Li,&nbsp;Xiaoying Chen,&nbsp;Zhuoxu Jiang,&nbsp;Jinyu Zhang,&nbsp;Yuan Zhuang,&nbsp;Yi Tian,&nbsp;Qingwu Yang,&nbsp;Alexei Verkhratsky,&nbsp;Ying Wan,&nbsp;Chenju Yi,&nbsp;Jianqin Niu","doi":"10.1126/scitranslmed.adn9980","DOIUrl":"10.1126/scitranslmed.adn9980","url":null,"abstract":"<div >Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelination and to developing early intervention strategies. Here, we aimed to model overactivated Wnt (wingless-related integration site) signaling previously shown in postmortem brain tissues of patients with MS by inducing experimental autoimmune encephalomyelitis (EAE) in <i>Pdgfra^CreER;Apc^fl/fl</i> and <i>Olig2^Cre;Apc^fl/fl</i> mice. These mice have overactivated Wnt signaling in oligodendrocyte precursor cells (OPCs) because of a conditional knockout of the pathway repressor adenomatous polyposis coli (APC). <i>Pdgfra^CreER;Apc^fl/fl</i> EAE mice exhibited increased expression of markers for Wnt activation such as Axis inhibition protein 2 (AXIN2) and Wnt inhibitory factor 1 (WIF1) in OPCs and showed exacerbated EAE progression in both the spinal cord and the brain. Genetic or antibody-mediated ablation of CC-chemokine ligand 4 (CCL4) prevented infiltration of CD4⁺ T cells and arrested disease progression in these mice. A characterization of CNS (central nervous system) immune cell clusters identified an augmented subpopulation of NK1.1⁺CD11b⁺Gr-1⁺ cytotoxic macrophages in <i>Pdgfra^CreER;Apc^fl/fl</i> EAE mice. Microinjection of this subpopulation of macrophages into the brains of wild-type C57/B6J mice was sufficient to induce demyelination. Ablation of CD4⁺ T cells prevented the effects of Wnt overactivation on demyelination and immune cell infiltration. Antagonizing chemokine receptor 5 (CCR5) using a European Medicines Agency–approved drug, maraviroc, reduced immune cell infiltration, alleviated demyelination, and attenuated EAE progression. We found an OPC-orchestrated immune cellular network that instigates early demyelination, provides insight into MS pathophysiology, and suggests avenues for early interventions.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 792","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human iPSC–derived nephron progenitor cells treat acute kidney injury and chronic kidney disease in mouse models","authors":"Toshikazu Araoka,&nbsp;Kosuke Toyohara,&nbsp;Makoto Ryosaka,&nbsp;Chihiro Inui,&nbsp;Maasa Matsuura,&nbsp;Chen Ma,&nbsp;Jun Watahiki,&nbsp;Zhongwei Li,&nbsp;Mio Iwasaki,&nbsp;Akira Watanabe,&nbsp;Ryuji Yokokawa,&nbsp;Yasuhiko Tabata,&nbsp;Juan Carlos Izpisua Belmonte,&nbsp;Kenji Osafune","doi":"10.1126/scitranslmed.adt5553","DOIUrl":"10.1126/scitranslmed.adt5553","url":null,"abstract":"<div >The number of patients requiring dialysis therapy continues to increase worldwide because of the lack of effective treatments for chronic kidney disease (CKD). Furthermore, no curative treatments for acute kidney injury (AKI) have been established. The therapeutic effects of human induced pluripotent stem cell–derived nephron progenitor cells (hiPSC-NPCs) on AKI have been reported in mice but not clinically confirmed. There are also no reports examining the therapeutic potential of hiPSC-NPCs on CKD. Although large numbers of uniform hiPSC-NPCs are required for cell therapies for AKI and CKD, effective expansion cultures remain to be developed. Here, we established a culture medium for cells that enabled more than 100-fold proliferation of hiPSC-NPCs from multiple hiPSC lines in two passages. We demonstrated that hiPSC-NPCs expanded by our medium named CFY or by their conditioned medium alone attenuated kidney injury and improved survival in cisplatin-induced AKI mice. We also observed that hiPSC-NPCs prevented kidney functional decline, interstitial fibrosis, and senescence in aristolochic acid–induced CKD mice. In addition, we found c-MET to be a specific cell surface marker for hiPSC-NPCs and confirmed that purified c-MET⁺ hiPSC-NPCs had therapeutic effects on AKI and CKD mice. Furthermore, we found that hiPSC-NPCs exerted their therapeutic effects in AKI and CKD mice by secreting vascular endothelial growth factor A. Expanded hiPSC-NPCs may be useful cell therapies for AKI and CKD and may open avenues for treating kidney diseases.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 792","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Path to a cure for debilitating pregnancy sickness","authors":"Marlena Fejzo","doi":"10.1126/scitranslmed.adw9351","DOIUrl":"10.1126/scitranslmed.adw9351","url":null,"abstract":"<div >Identification of GDF15 as a cause of severe nausea and vomiting during pregnancy is opening new doors for treatment and prevention.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 792","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mavoglurant reduces cocaine use in patients with cocaine use disorder in a phase 2 clinical trial","authors":"Baltazar Gomez-Mancilla,&nbsp;Kenneth M. Dürsteler,&nbsp;Marc Vogel,&nbsp;Marcus Herdener,&nbsp;Marta Torrens,&nbsp;Bartolomé P. Gálvez,&nbsp;Antoni Gual,&nbsp;Ricardo M. Corral,&nbsp;Enrique I. Kuper,&nbsp;Daniel L. Mosca,&nbsp;Swati Dumitras,&nbsp;Nicole Pezous,&nbsp;Maria Berkheimer,&nbsp;Ela Walker,&nbsp;Fabrizio Gasparini,&nbsp;Jang-Ho Cha,&nbsp;Ricardo Dolmetsch","doi":"10.1126/scitranslmed.adi4505","DOIUrl":"10.1126/scitranslmed.adi4505","url":null,"abstract":"<div >Metabotropic glutamate receptor 5 (mGluR5) is involved in cocaine reward processing and addiction. Preclinical studies suggest that blocking this receptor inhibits cocaine self-administration and seeking behavior in rodents. We assessed a selective noncompetitive antagonist of mGluR5 called mavoglurant in a phase 2 randomized, placebo-controlled clinical trial of 68 adults with cocaine use disorder. Study participants were randomly assigned in a 1:1 ratio to an up-titrating schedule of oral mavoglurant twice daily up to 200 mg for 98 days or placebo. The primary end point was the proportion of cocaine use days over the treatment period assessed by a retrospective self-report using Timeline Followback. Secondary end points were urine analysis of the cocaine metabolite benzoylecgonine and alcohol use measured by Timeline Followback assessment. Exploratory end points included testing for cocaine and alcohol metabolites in hair samples. The posterior probability of mavoglurant reducing cocaine use at the end of treatment was ≥99.0% for a treatment difference &lt;0 and ≥36.6% for a treatment difference &lt;−10%. The difference between mavoglurant and placebo was also assessed using analysis of covariance (<i>P</i> = 0.021). Urine benzoylecgonine concentration was lower in the mavoglurant-treated group versus placebo (<i>P</i> = 0.025); there was reduced alcohol consumption in the treatment group (<i>P</i> = 0.072). Seventy-six percent (randomized set) and 79% (safety analysis set) of patients completed the final treatment visit. Adverse events in the treatment group were headache, dizziness, and nausea. In this small and short trial, mavoglurant reduced cocaine and alcohol use in patients with chronic cocaine use disorder.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 792","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically compliant enrichment of human pluripotent stem cell–derived islets","authors":"Bahareh Rajaei,&nbsp;Amadeo Muñoz Garcia,&nbsp;Juri Juksar,&nbsp;Jason B. Doppenberg,&nbsp;Miriam Paz-Barba,&nbsp;Fransje Boot,&nbsp;Willemijn de Vos,&nbsp;Aat A. Mulder,&nbsp;Ferdy Lambregtse,&nbsp;Lizanne Daleman,&nbsp;Anne E. de Leeuw,&nbsp;Maaike C. Nieveen,&nbsp;Marten A. Engelse,&nbsp;Ton Rabelink,&nbsp;Eelco J. P. de Koning,&nbsp;Françoise Carlotti","doi":"10.1126/scitranslmed.adl4390","DOIUrl":"10.1126/scitranslmed.adl4390","url":null,"abstract":"<div >Human pluripotent stem cell–derived islet (SC-islet) transplantation is a promising β cell replacement therapy for patients with type 1 diabetes, offering a potential unlimited cell supply. Yet, the heterogeneity of the final cell product containing non–target cell types has relevant implications for SC-islet function, transplant volume, and cell product safety. Here, we present a clinically compliant, full three-dimensional differentiation protocol that includes a purification step of endocrine cell–rich clusters, relying on the principle of isopycnic centrifugation (density gradient separation). Enriched SC-islets displayed signs of functionality in vitro and in vivo. In contrast with antibody-based single-cell sorting approaches, this method does not destroy the islet cytoarchitecture associated with alterations of islet function and cell loss. Furthermore, it is fast, is easily scalable to large cell volumes, and can be applied during cell manufacturing. This method may also contribute to the generation of improved cell-based therapies for regenerative medicine purposes beyond the SC-islet field.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 792","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome","authors":"Paul D. Ross,&nbsp;Kamal K. E. Gadalla,&nbsp;Sophie R. Thomson,&nbsp;Jim Selfridge,&nbsp;Noha G. Bahey,&nbsp;Juliana Benito,&nbsp;Suzanne R. Burstein,&nbsp;Rachel McMinn,&nbsp;Brad Bolon,&nbsp;Ralph D. Hector,&nbsp;Stuart R. Cobb","doi":"10.1126/scitranslmed.adq3614","DOIUrl":"10.1126/scitranslmed.adq3614","url":null,"abstract":"<div >Conventional methods of gene transfer lead to inconsistent transgene expression within cells. This variability can be problematic, particularly in conditions like Rett syndrome (RTT), a neurological disorder caused by mutations in the <i>MECP2</i> (methyl-CpG binding protein 2) gene, because overexpression of <i>MECP2</i> can also cause adverse effects. To address these challenges, we devised a gene regulation system called Expression Attenuation via Construct Tuning (EXACT), which uses a self-contained, microRNA-based feed-forward loop that not only ensures more consistent transgene expression but also protects against excessive expression. Through cell-based screening assays, we demonstrated the ability of the EXACT circuit to modulate the expression of full-length human MeCP2. Compared with a conventional construct, an EXACT-<i>MECP2</i> construct exhibited a narrower range of cellular protein abundance. Furthermore, the degree of regulation by the EXACT circuit increased with higher transgene doses in vitro and in wild-type mice and mice modeling RTT. On the basis of cellular and in vivo testing, we identified an optimal configuration for the adeno-associated virus serotype 9 (AAV9) construct for self-regulated <i>MECP2</i> gene therapy, designated NGN-401. Delivery of NGN-401 to neonatal male <i>Mecp2^−/y</i> hemizygous mice via intracerebroventricular injection resulted in prolonged survival and amelioration of RTT-like phenotypes compared with vehicle-treated animals. NGN-401 was also well tolerated by female <i>Mecp2^+/−</i> mice and healthy juvenile nonhuman primates, in contrast with a conventional construct, which caused toxicity. The results from these studies underpin a first-in-human pediatric trial of NGN-401 in RTT (ClinicalTrials.gov, NCT05898620).</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 792","pages":""},"PeriodicalIF":15.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}