tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Zanubrutinib in Immune Thrombocytopenia
Authors: Qiu‐Sha Huang, Hai‐Xia Fu, Chen‐Cong Wang, Xiao‐Lu Zhu, Yun He, Jin Wu, Qi Chen, Peng Zhao, Zhuo‐Yu An, Kai‐Yan Liu, Xiao‐Jun Huang, Xiao‐Hui Zhang
Journal: American Journal of Hematology (2025)

ABSTRACT Immune thrombocytopenia (ITP) is characterized by impaired platelet production and increased platelet destruction. Zanubrutinib is a highly selective next‐generation Bruton tyrosine kinase (BTK) inhibitor that may reduce autoantibody production and reduce macrophage Fcγ receptor‐mediated platelet destruction. In this single‐arm, phase II study, we aimed to assess the efficacy and safety of zanubrutinib in corticosteroid‐resistant or relapsed ITP. All patients received 80 mg zanubrutinib once daily for 6 weeks followed by a 20‐week safety follow‐up period. The primary endpoint was overall response (OR), defined as at least two consecutive platelet counts of at least 30 × 10 9 /L, at least a 2‐fold increase in the baseline count, the absence of bleeding, and no need for rescue therapy at 4 weeks. The trial was registered with ClinicalTrials.gov , number NCT05279872. Between January 1, 2022 and October 30, 2022, 20 patients were enrolled. The median platelet count was 19 (10–25) × 10 9 /L at the time of enrollment. Participants had received a median of 4 (3–6) different therapies for ITP. Eleven (55%, 95% CI: 31.5%–76.9%) patients achieved an OR to the intervention. Two (10%) patients achieved a complete response. At the 6‐month follow‐up, a sustained response was achieved in seven (35.0%, 95% CI: 15.4%–59.2%) patients. There were no grade 4 or worse adverse events or treatment‐related deaths. The most common adverse events were upper respiratory tract infection (in 25% of the patients). Zanubrutinib showed an encouraging response rate and tolerability, supporting its therapeutic potential for the treatment of ITP. Trial Registration: ClinicalTrials.gov identifier: NCT05279872.
Evaluation of exposure‐response‐safety relationship of model‐informed low‐dose 500 mg abiraterone acetate in prostate cancer patients
Authors: Edmund Chiong, Ziteng Wang, Eleanor Jing Yi Cheong, Yi Chen Yao, Sin Mun Tham, Revathi Periaswami, Poh Choo Toh, Ziting Wang, Qing Hui Wu, Woon Chau Tsang, Arshvin Kesavan, Alvin Seng Cheong Wong, Patrick Thomas Wong, Felicia Lim, Shuaibing Liu, Eric Chun Yong Chan
Journal: Cancer Communications (2025)
Economic Impact of Allergic Diseases and Asthma—The <scp>HEAD</scp> Pan‐European Registry
Authors: Ioana Agache, Maria Torres, Ibon Eguiluz‐Gracia, Elena Bradatan, Kamal El Abd, Maria Beatrice Bilo, Federica Rivolta, Andrea Sangalli, Roxana Bumbacea, Selda Ali, Dario Antolin, Águeda Concepción Lario Cuenda, Vicente Albéndiz, Maria Miguel Oliveira, Paulo Jorge Nogueira, Loreto Carmona
Journal: Allergy (2025)

ABSTRACT The Health Economics of Allergic Diseases (HEAD) registry is a European‐based registry developed by the European Academy of Allergy and Clinical Immunology in collaboration with national allergy societies to facilitate standardised allergic disease management. Using an observational design, this first registry‐based study describes care patterns for allergic diseases and their impact on the healthcare system (diagnostic and management costs), society (missed work/school days and disability pension/support) and patients (out‐of‐pocket costs) in 778 adults and children with allergic rhinitis, asthma, atopic dermatitis and food allergy, from four countries (Belgium, Italy, Romania and Spain). The average total costs per patient and per year were €1329.55 ± 1947.39, with indirect costs of €338.68 ± 1629.61. Direct costs consisted of €82.74 ± 585.90 for hospitalisations, €17.50 ± 125.07 for the emergency department, €172.94 ± 323.17 for specialists, €22.70 ± 132.42 for primary care, €4.85 ± 136.84 for psychologists, €21.24 ± 82.47 for diagnosis and €104.81 ± 469.26 for treatments. Indirect costs were out‐of‐pocket consultation fees (€16.24 ± 106.40), medications (€161.90 ± 710.58), transportation (€44.15 ± 218.51), private insurance (€16.77 ± 157.91), avoidance (€8.65 ± 92.99) and environmental control (€99.33 ± 955.23). Adults missed 1.02 ± 3.20 workdays, children missed 0.53 ± 2.18 schooldays and burdened their families with 1.38 ± 13.83 lost days. There was a high degree of heterogeneity across countries for management patterns and for costs. The significant burden of allergic diseases calls for immediate action for better management.
Linking Exosomal <scp>MicroRNA</scp> Signatures in Sputum and Peripheral Blood to Inflammatory Endotypes in Severe Asthma
Authors: D. Sanz‐Rubio, E. Vera, J. Rodríguez‐Sanz, J. Cubero, R. Langarita, M. Aguado, L. Pastor, L. Martín, M. Marín‐Oto, A. R. Remacha, M. Ruiz, V. Gil, J. A. Domingo, J. A. Carretero, J. M. Marín
Journal: Allergy (2025)
Targeted reactivation of the novel tumor suppressor DAPK1, an upstream regulator of p53, in high‐grade serous ovarian cancer by mRNA liposomes reduces viability and enhances drug sensitivity in preclinical models
Authors: Monika Raab, Balázs Győrffy, Samuel Peña‐Llopis, Daniela Fietz, Monika Kressin, Margareta Kolaric, Matthias Ebert, Khayal Gasimli, Sven Becker, Mourad Sanhaji, Klaus Strebhardt
Journal: Cancer Communications (2025)
The Standardized Outcomes in Nephrology (SONG) initiative: a decade of harmonizing patient voices and research in kidney disease
Authors: Colm O'Reilly, Jonathan C Craig, Younghee Cho, Sally Crowe, John S Gill, Brenda Hemmelgarn, Martin Howell, Anastasia Hughes, Angela Ju, Karine Manera, Braden Manns, Roberto Pecoits-Filho, Benedicte Sautenet, Nicole Scholes-Robertson, Armando Teixeira-Pinto, Peter Tugwell, Wim Van Biesen, Andrea K Viecelli, Angela Yee-Moon Wang, Wolfgang C Winkelmayer, Germaine Wong, Chandana Guha, Allison Jaure
Journal: Kidney International (2025)
Corrigendum to “Effects of dialysate potassium concentration of 3.0 mmol/l with sodium zirconium cyclosilicate on dialysis-free days versus dialysate potassium concentration of 2.0 mmol/l alone on rates of cardiac arrhythmias in hemodialysis patients with hyperkalemia.” Kidney International 2025;107:169–179
Authors: David M Charytan, Wolfgang C Winkelmayer, Christopher B Granger, John P Middleton, Charles A Herzog, Glenn M Chertow, James M Eudicone, Jeremy D Whitson, James A Tumlin
Journal: Kidney International (2025)
CloseRead: a tool for assessing assembly errors in immunoglobulin loci applied to vertebrate long-read genome assemblies
Authors: Yixin Zhu, Corey Watson, Yana Safonova, Matt Pennell, Anton Bankevich
Journal: Genome biology (2025)

Abstract Despite tremendous advances in long-read sequencing, some structurally complex and repeat-rich genomic regions remain challenging to assemble. Furthermore, we lack tools to assess local assembly quality, making it hard to identify problems and assess progress. Here we develop a new approach “CloseRead” for visualizing local assembly quality and diagnosing errors using multiple metrics. We apply CloseRead to evaluate how well immunoglobulin loci, paradigmatic cases of structurally complex regions, are assembled in 74 state-of-the-art vertebrate genomes. We then show that targeted, local re-assembly can correct the specific errors identified by CloseRead, highlighting the value of an iterative approach to genome assembly.
CMImpute: cross-species and tissue imputation of species-level DNA methylation samples across mammalian species
Authors: Emily Maciejewski, Steve Horvath, Jason Ernst
Journal: Genome biology (2025)

Abstract The large-scale application of the mammalian methylation array has substantially expanded the availability of DNA methylation data in mammalian species. However, this data captures only a small portion of species-tissue combinations. To address this, we develop CMImpute (Cross-species Methylation Imputation), a method based on a conditional variational autoencoder, to impute DNA methylation representing species-tissue combinations. We demonstrate that CMImpute achieves strong sample-wise correlation between imputed and observed values. Using CMImpute and data from 348 species and 59 tissue types, we impute methylation data for 19,786 new species-tissue combinations. We expect CMImpute will be a useful resource for DNA methylation analyses.
Trajectories from single-cells to PAX5-driven leukemia reveal PAX5-MYC interplay in vivo
Authors: Franziska Auer, Mina N F Morcos, Mikko Sipola, Irfan Akhtar, Sanni Moisio, Julia Vogt, Rebecca Haag, Mari Lahnalampi, Tiina J Tuononen, Andrea Hanel, Anna Viitasalo, Ulrike A Friedrich, Andreas Dahl, Carolin Prexler, Aleksandra A Pandyra, Polina Stepensky, Masatoshi Takagi, Arndt Borkhardt, Merja Heinäniemi, Julia Hauer
Journal: Leukemia (2025)

Abstract PAX5 acts as a master regulator of B-cell proliferation and differentiation. Its germline and somatic deregulation have both been implicated in the development of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the process how reduced PAX5 transcriptional activity mediates progression to BCP-ALL, is still poorly understood. Here, we characterized the longitudinal effects of PAX5 reduction on healthy, pre-leukemic and BCP-ALL cells at the single-cell level. Cell-surface marker analysis revealed a genotype-driven enrichment of the pre-BII population in healthy Pax5 ± mice. This population showed downregulated B-cell receptor signaling, while DNA replication/repair and cell-cycle signaling pathways were upregulated. Moreover, we observed a shift in the kappa/lambda light chain ratio toward lambda rearranged B-cells. Transplantation experiments further validated a delay of Pax5 ± pre-BII cells in maturation and transition to IgM-positivity. Additionally, single-cell RNA-Sequencing and bulk ATAC-Sequencing of different stages of BCP-ALL evolution showed that Pax5 ± pre-leukemic cells lose their B-cell identity and display Myc activation. Subsequently, BCP-ALLs acquired additional RAG-mediated aberrations and driver mutations in JAK-STAT and RAS-signaling pathways. Together, this study elucidates molecular and functional checkpoints in PAX5-mediated pre-leukemic cell progression exploitable for therapeutic intervention and demonstrates that PAX5 reduction is sufficient to initiate clonal evolution to BCP-ALL through activation of MYC.
Nuclear SREBP2 condensates regulate the transcriptional activation of lipogenic genes and cholesterol homeostasis
Authors: Mengqiang Xu, Shi-You Jiang, Shuocheng Tang, Meimei Zhu, Yueer Hu, Juewan Li, Jizhi Yan, Chenyang Qin, Dongxia Tan, Yang An, Yuxiu Qu, Bao-Liang Song, Hanhui Ma, Wei Qi
Journal: Nature Metabolism (2025)
Cancer treatment paradigms in the precision medicine era
Authors: Vivek Subbiah, Giuseppe Curigliano, Jason K Sicklick, Shumei Kato, Kjetil Tasken, Arielle Medford, Damian T Rieke, Hui-Zi Chen, Adam Wahida, Lars Buschhorn, Denis Horgan, Razelle Kurzrock
Journal: Nature Medicine (2025)
Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs
Authors: Zheng Hu, Jun Zou, Zhengzhu Wang, Kai Xu, Tang Hai, Sheng Zhang, Peipei An, Cong Fu, Shuai Dong, Yanan Lv, Jilong Ren, Zhiqiang Han, Chongyang Li, Jing Wang, Qingwei Wang, Renren Sun, Long Su, Hanjing Zuo, Qinghao Ding, Huimin Tian, Xinlan An, Yanhui Zhai, Dawei Yu, Chang Shu, Jin He, Liguang Sun, Tianmeng Sun, Xiangpeng Dai, Ziyi Li, Wei Li, Qi Zhou, Yong-Guang Yang
Journal: Nature Biomedical Engineering (2025)
Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure
Authors: Helen Carrasco Hope, Jana de Sostoa, Pierpaolo Ginefra, Massimo Andreatta, Yi-Hsuan Chiang, Catherine Ronet, Christine Pich-Bavastro, Jesús Corria Osorio, François Kuonen, Johan Auwerx, Patrizia D'Amelio, Ping-Chih Ho, Santiago J Carmona, George Coukos, Denis Migliorini, Nicola Vannini
Journal: Nature Cancer (2025)
Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer’s disease
Authors: Gyujin Heo, Ying Xu, Erming Wang, Muhammad Ali, Hamilton Se-Hwee Oh, Patricia Moran-Losada, Federica Anastasi, Armand González Escalante, Raquel Puerta, Soomin Song, Jigyasha Timsina, Menghan Liu, Daniel Western, Katherine Gong, Yike Chen, Pat Kohlfeld, Allison Flynn, Alvin G Thomas, Joseph Lowery, John C Morris, David M Holtzman, Joel S Perlmutter, Suzanne E Schindler, Natalia Vilor-Tejedor, Marc Suárez-Calvet, Pablo García-González, Marta Marquié, Maria Victoria Fernández, Mercè Boada, Amanda Cano, Agustín Ruiz, Bin Zhang, David A Bennett, Tammie Benzinger, Tony Wyss-Coray, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga
Journal: Nature Aging (2025)
Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice
Authors: Yun Zhang, Huaqiu Chen, Yijia Feng, Mingjing Liu, Zhi Lu, Bolang Hu, Lifen Chen, Yang Zhang, Jiawen Liu, Fang Cai, Yifan Zhao, Wenhao Pan, Xinxin Liao, Sipei Pan, Isabel Bestard-Lorigados, Yili Wu, Weihong Song
Journal: Nature Aging (2025)
Treatment of a metabolic liver disease in mice with a transient prime editing approach
Authors: Tanja Rothgangl, András Tálas, Eleonora I Ioannidi, Yanik Weber, Desirée Böck, Mai Matsushita, Elina Andrea Villiger, Lukas Schmidheini, Woohyun J Moon, Paulo J C Lin, Steven H Y Fan, Kim F Marquart, Cornelia Schwerdel, Nicole Rimann, Erica Faccin, Lukas Villiger, Hiromi Muramatsu, Máté Vadovics, Alessio Cremonesi, Péter István Kulcsár, Beat Thöny, Manfred Kopf, Johannes Häberle, Norbert Pardi, Ying K Tam, Gerald Schwank
Journal: Nature Biomedical Engineering (2025)
High-throughput single-cell density measurements enable dynamic profiling of immune cell and drug response from patient samples
Authors: Weida Wu, Sarah H Ishamuddin, Thomas W Quinn, Smitha Yerrum, Ye Zhang, Lydie L Debaize, Pei-Lun Kao, Sarah Marie Duquette, Mark A Murakami, Morvarid Mohseni, Kin-Hoe Chow, Teemu P Miettinen, Keith L Ligon, Scott R Manalis
Journal: Nature Biomedical Engineering (2025)
Correction: Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel™) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study
Authors: Gaurav Narula, Swaminathan Keerthivasagam, Hasmukh Jain, Sachin Punatar, Akanksha Chichra, Chetan Dhamne, Prashant Tembhare, Papagudi Ganesan Subramanian, Nikhil Patkar, Minal Poojary, Anant Gokarn, Sumeet Mirgh, Nishant Jindal, Albeena Nisar, Deepali Pandit, Khushali Pandit, Alka Dwivedi, Atharva Karulkar, Ankesh Kumar Jaiswal, Aalia Khan, Shreshtha Shah, Afrin Rafiq, Moumita Basu, Juber Pendhari, Sweety Asija, Ambalika Chowdury, Ankit Banik, Nirmalya Roy Moulik, Shyam Srinivasan, Shilpushp Bhosle, Sumathi Hiregoudar, Shashank Ojha, Lingaraj Nayak, Jayshree Thorat, Bhausaheb Bagal, Manju Sengar, Navin Khattry, Shripad Banavali, Steven Highfill, Nirali N Shah, Rahul Purwar
Journal: Blood Cancer Journal (2025)
A multivariate model incorporating subharmonic measurements for evaluating vocal roughness
Authors: Itsuki Kitayama, Kiyohito Hosokawa, Shinobu Iwaki, Misao Yoshida, Akira Miyauchi, Kenji Aruga, Takanari Kawabe, Toshihiro Kishikawa, Hidenori Tanaka, Takeshi Tsuda, Takashi Sato, Yukinori Takenaka, Makoto Ogawa, Hidenori Inohara
Journal: npj Digital Medicine (2025)
10-Year Outcome of Complete or Infarct–Artery-Only Revascularization in STEMI with Multivessel Disease (DANAMI-3-PRIMULTI)
Authors: Jasmine M Marquard, Rasmus P Beske, Henning Kelbæk, Lene Holmvang, Frants Pedersen, Peter Clemmensen, Ole De Backer, Bent Raungaard, Ashkan Eftekhari, Utsho Islam, Lars Køber, Hans-Henrik Tilsted, Charlotte Glinge, Reza Jabbari, Thomas Scheike, Dan E Høfsten, Jacob T Lønborg, Thomas Engstrøm
Journal: Journal of the American College of Cardiology (2025)
Induction of p53-mediated apoptosis by azacitidine in patient-derived xenograft follicular helper T-cell lymphoma model
Authors: Gamze Tari Crochet, Selcen Ari-Yuka, Anja Fischer, Mohamed Chour, Alexis Claudel, Nouhoum Sako, Cyrielle Robe, Julie Naudet, Alexis Gonon, Diana Laure Mboumba, Nicolas Ortonne, Vincent Alcazer, Marie-Hélène Delfau-Larue, Reiner Siebert, Philippe Gaulard, François Lemonnier
Journal: Leukemia (2025)
<scp>AI</scp>‐Based Objective Severity Assessment of Atopic Dermatitis Using Patient Photos in a Real‐World Setting: A Digital Biomarker Approach
Authors: Utako Okata‐Karigane, Masakazu Hirota, Chiaki Takahashi, Akihiro Miyagawa, Ryotaro Ako, Saeko Nakajima, Masaki Futamura, Satoru Yonekura, Yasushi Ogawa, Takenori Inomata, Tetsuo Ishikawa, Yoshihiro Ito, Katsunori Masaki, Sakura Sato, Norito Katoh, Hideaki Morita, Takeya Adachi
Journal: Allergy (2025)
Mutational signatures and kataegis in pediatric B‐cell precursor acute lymphoblastic leukemia
Authors: Rebeqa Gunnarsson, Minjun Yang, Andrea Biloglav, Kristina B. Lundin‐Ström, Henrik Lilljebjörn, Anders Castor, Thoas Fioretos, Linda Olsson‐Arvidsson, Kajsa Paulsson, Bertil Johansson
Journal: HemaSphere (2025)
Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis
Authors: Min-Young Noh, Seong-Il Oh, Young-Eun Kim, Sun Joo Cha, Wonjae Sung, Ki-Wook Oh, Yurim Park, Ji Young Mun, Chang-Seok Ki, Minyeop Nahm, Seung Hyun Kim
Journal: Molecular Neurodegeneration (2025)
Spleen-Heart Cross-Talk Through CD23-Mediated Signal Promotes Cardiac Remodeling
Authors: Yufan Feng, Yang Yang, Hongqin Yang, Jin Shan, Jiaxin Zhang, Qian Chen, Yingge Zhang, Yarong Zhang, Zhiwei Li, Yunfei Xue, Junye Chen, Chi Geng, Kegang Jia, Hongmei Zhao, Jing Wang
Journal: Circulation Research (2025)

BACKGROUND: Elevated levels of IgE are implicated in pathological cardiac remodeling. However, the origin of IgE remains unknown. In the current study, we aim to explore the source of IgE and the mechanisms underlying IgE production in the context of pathological cardiac remodeling. METHODS: Flow cytometry was used to assess the changes of IgE-producing B cells in different organs/tissues, including the spleen, lymph nodes, bone marrow, peripheral blood, vasculature, and heart, in mice with cardiac remodeling induced by transverse aortic constriction (TAC). The role of IgE low-affinity receptor FcεRII (also named CD23) in IgE-producing B cells during cardiac remodeling was evaluated in mice with loss-of-CD23 or gain-of-CD23. The therapeutic potential of the CD23-neutralizing antibody was evaluated. The factors involved in organ cross-talk, which regulate IgE production, were identified and validated both in vitro and in vivo. RESULTS: We found that splenic IgE-producing cells were significantly elevated in the TAC mice. CD23, as a negative regulator of IgE production, was decreased in splenic B cells of TAC mice. Global knockout of CD23 in mice aggravated TAC-induced IgE synthesis and cardiac remodeling in vivo. In contrast, global or B-cell–specific CD23 overexpression in mice reduced IgE synthesis and alleviated TAC-induced cardiac remodeling. Mechanistically, CD23 was cleaved by ADAM10 (A disintegrin and metalloproteinase domain 10) in the spleen. Screening assay with data-independent acquisition mass spectrometry–based proteomics and ELISA identified Ltf (lactotransferrin), released from the heart shortly after TAC stimulation, as a contributor to ADAM10 upregulation through binding to Ltf receptor Ncl (nucleolin). Meanwhile, Ltf administration promoted IgE elevation, accompanied by increased ADAM10 expression and decreased CD23 expression in vitro and in vivo. Furthermore, the plasma Ltf levels were positively correlated with TAC-induced cardiac remodeling, serum IgE, and sCD23 (soluble CD23). Consistently, Ltf levels were elevated in patients with heart failure with reduced ejection fraction and also positively correlated with serum IgE and sCD23. CONCLUSIONS: Our findings indicate a critical role of the Ltf-ADAM10-CD23 axis in regulating IgE production through cross-talk between the heart and spleen. The Ltf-ADAM10-CD23 axis may represent new molecular targets for IgE-mediated pathological cardiac remodeling.
Spatio-temporal T cell tracking for personalized TCR-T designs in childhood cancer
Authors: I Sentís, J L Melero, A Cebria-Xart, M Grzelak, M Soto, A Michel, Q Rovira, C J Rodriguez-Hernandez, G Caratù, A Urpi, C Sauvage, A Mendizabal-Sasieta, D Maspero, C E Lavarino, A Pascual-Reguant, A Castañeda Heredia, J P Muñoz Perez, J Mora, A Harari, J C Nieto, A Avgustinova, H Heyn
Journal: Annals of Oncology (2025)
Efficacy and Safety of Inclisiran in Adolescents With Genetically Confirmed Homozygous Familial Hypercholesterolemia: Results From the Double-Blind, Placebo-Controlled Part of the ORION-13 Randomized Trial
Authors: Albert Wiegman, Amy L. Peterson, Robert A. Hegele, Eric Bruckert, Anja Schweizer, Anastasia Lesogor, Yibo Wang, Joep Defesche
Journal: Circulation (2025)

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a genetic disease characterized by high levels of low-density lipoprotein cholesterol (LDL-C) present from birth, leading to early-onset and progressive atherosclerotic cardiovascular disease. Early treatment initiation is crucial for cardiovascular risk reduction; however, many patients do not reach LDL-C treatment goals. Inclisiran, a small interfering RNA targeting hepatic PCSK9 (proprotein convertase subtilisin/kexin type 9), is effective and well tolerated in adult patients with hyperlipidemia; however, it has not yet been studied in pediatric patients. METHODS: Herein we report results of the 1-year, double-blind, placebo-controlled part of the phase 3 study ORION-13 (Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia) in adolescents with HoFH. This 2-part multicenter study included 13 patients ≥12 to &lt;18 years of age with a genetic diagnosis of HoFH (excluding LDL [low-density lipoprotein] receptor [ LDLR ] null/null genotypes) and elevated LDL-C levels (&gt;130 mg/dL) on maximally tolerated statin treatment, with or without other lipid-lowering therapies. Eligible patients were randomized 2:1 to receive either 300 mg of inclisiran sodium or placebo, administered on days 1, 90, and 270. The primary end point was the mean percentage change in LDL-C from baseline to day 330. RESULTS: The mean age of patients was 14.8 years, and mean baseline LDL-C was 272 mg/dL. The placebo-adjusted mean (95% CI) percentage change in LDL-C from baseline to day 330 was −33.3% (−59.2% to −7.3%). Six of 9 (66.7%) inclisiran-treated patients (versus 1 of 4 [25%] on placebo) achieved a &gt;15% reduction in LDL-C, and 5 of 9 (55.6%) inclisiran-treated patients (versus none on placebo) achieved a &gt;20% reduction. The placebo-adjusted mean (95% CI) percentage change in PCSK9 from baseline to day 330 was −60.2% (−79.8% to −40.7%); corresponding changes in apoB (apolipoprotein B), non–high-density lipoprotein cholesterol, and total cholesterol were −23.0%, −32.7%, and −27.8%, respectively. No serious adverse events, treatment discontinuations because of adverse events, or deaths occurred. No new safety findings were reported. CONCLUSIONS: In a 1-year randomized controlled study (part 1 of ORION-13), inclisiran was effective in lowering LDL-C in adolescents with HoFH and was well tolerated. These results support inclisiran as a potentially useful addition for the treatment of adolescents with HoFH and a minimum of LDLR residual activity. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04659863.