Med最新文献

{"title":"How to rescue a DreaMM deferred ….","authors":"Nisha S Joseph, Sagar Lonial","doi":"10.1016/j.medj.2024.07.027","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.027","url":null,"abstract":"<p><p>The recently published DreaMM-7 and -8 trials¹^,² demonstrate the benefit of triplet combination regimens including the anti-BCMA antibody drug conjugate belantamab mafodotin. Here, we describe the findings of these trials including efficacy and safety data and provide commentary on the implications for future use of belantamab in the relapsed myeloma space.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 9","pages":"1048-1049"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR-mutated NSCLC: A roadmap to treatment sequences.","authors":"Nicolas Girard","doi":"10.1016/j.medj.2024.07.010","DOIUrl":"10.1016/j.medj.2024.07.010","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for the management of EGFR-mutated non-small cell lung cancer. Recent results from the HARMONi-A trial lead to considering ivonescimab-a first-in-class, bispecific antibody targeting PD-1 and VEGF-plus chemotherapy as a new second-line option following third-generation TKIs.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"5 9","pages":"1044-1047"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC.","authors":"Hideaki Bando, Daisuke Kotani, Hironaga Satake, Tetsuya Hamaguchi, Manabu Shiozawa, Masahito Kotaka, Toshiki Masuishi, Hisateru Yasui, Yoshinori Kagawa, Yoshito Komatsu, Eiji Oki, Yoshiyuki Yamamoto, Hisato Kawakami, Toshihiro Misumi, Hiroya Taniguchi, Kentaro Yamazaki, Kei Muro, Takayuki Yoshino, Takeshi Kato, Akihito Tsuji","doi":"10.1016/j.medj.2024.05.012","DOIUrl":"10.1016/j.medj.2024.05.012","url":null,"abstract":"<p><strong>Background: </strong>The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC).</p><p><strong>Methods: </strong>In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes.</p><p><strong>Findings: </strong>Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%).</p><p><strong>Conclusion: </strong>CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC.</p><p><strong>Funding: </strong>Chugai Pharmaceutical Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1164-1177.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study.","authors":"Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Di An, Kathie M Bishop, James M Youakim","doi":"10.1016/j.medj.2024.05.018","DOIUrl":"10.1016/j.medj.2024.05.018","url":null,"abstract":"<p><strong>Background: </strong>Trofinetide was approved for the treatment of Rett syndrome based on the results of the phase 3, randomized, placebo-controlled, 12-week LAVENDER study. Rett syndrome is a chronic disorder requiring long-term treatment. We report the efficacy and safety results of LILAC, a 40-week, open-label extension study of LAVENDER.</p><p><strong>Methods: </strong>Females with Rett syndrome aged 5-21 years received open-label treatment with trofinetide for 40 weeks. The primary endpoint was long-term safety of trofinetide; secondary endpoints included the change from baseline at week 40 in the Rett Syndrome Behaviour Questionnaire score and the Clinical Global Impression-Improvement score at week 40.</p><p><strong>Findings: </strong>Overall, 154 participants were enrolled and treated with trofinetide in LILAC. The most common adverse events in LILAC were diarrhea (74.7%), vomiting (28.6%), and COVID-19 (11.0%). Diarrhea was the most common adverse event leading to treatment withdrawal (21.4%). The Rett Syndrome Behaviour Questionnaire mean score (standard error) improvement from the LAVENDER baseline to week 40 in LILAC was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean Clinical Global Impression-Improvement scores (standard error) at week 40 rated from the LILAC baseline were 3.1 (0.11) and 3.2 (0.14) for participants treated with trofinetide and placebo in LAVENDER, respectively.</p><p><strong>Conclusions: </strong>Treatment with trofinetide for ≤40 weeks continued to improve symptoms of Rett syndrome. Trofinetide had a similar safety profile in LILAC as in LAVENDER.</p><p><strong>Funding: </strong>The study was supported by Acadia Pharmaceuticals Inc. (San Diego, CA, USA). This trial was registered at ClinicalTrials.gov (NCT04279314).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1178-1189.e3"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adding first-line PD-1 inhibition to anti-VEGF and XELOX in pMMR metastatic colorectal cancer: Steppingstones, stumbling blocks, and next phase.","authors":"Torhild Veen, Kjetil Søreide","doi":"10.1016/j.medj.2024.06.006","DOIUrl":"10.1016/j.medj.2024.06.006","url":null,"abstract":"<p><p>In the randomized, double-blind, multicenter study by Wang et al.,¹ the addition of serplulimab (a PD-1 antibody) to anti-VEGF (HLX04; a bevacizumab biosimilar) together with chemotherapy (XELOX) was deemed to be tolerable and safe and may improve progression-free survival. However, even if adverse events were comparable, oncological endpoints including survival need to be confirmed in the next phase 3 study.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1041-1043"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating drug discovery, development, and clinical trials by artificial intelligence.","authors":"Yilun Zhang, Mohamed Mastouri, Yang Zhang","doi":"10.1016/j.medj.2024.07.026","DOIUrl":"10.1016/j.medj.2024.07.026","url":null,"abstract":"<p><p>Artificial intelligence (AI) has profoundly advanced the field of biomedical research, which also demonstrates transformative capacity for innovation in drug development. This paper aims to deliver a comprehensive analysis of the progress in AI-assisted drug development, particularly focusing on small molecules, RNA, and antibodies. Moreover, this paper elucidates the current integration of AI methodologies within the industrial drug development framework. This encompasses a detailed examination of the industry-standard drug development process, supplemented by a review of medications presently undergoing clinical trials. Conclusively, the paper tackles a predominant obstacle within the AI pharmaceutical sector: the absence of AI-conceived drugs receiving approval. This paper also advocates for the adoption of large language models and diffusion models as a viable strategy to surmount this challenge. This review not only underscores the significant potential of AI in drug discovery but also deliberates on the challenges and prospects within this dynamically progressing field.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"1050-1070"},"PeriodicalIF":12.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DEBBRAH trial: Trastuzumab deruxtecan in HER2-positive and HER2-low breast cancer patients with leptomeningeal carcinomatosis.","authors":"Marta Vaz Batista, José Manuel Pérez-García, Laia Garrigós, José Ángel García-Sáenz, Patricia Cortez, Fabricio Racca, Salvador Blanch, Manuel Ruiz-Borrego, Adela Fernández-Ortega, María Fernández-Abad, Vega Iranzo, María Gion, Griselda Martrat, Daniel Alcalá-López, Jhudit Pérez-Escuredo, Miguel Sampayo-Cordero, Antonio Llombart-Cussac, Sofia Braga, Javier Cortés","doi":"10.1016/j.medj.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.medj.2024.08.001","url":null,"abstract":"<p><strong>Background: </strong>Leptomeningeal disease (LMD) is associated with poor survival and diminished quality of life. Trastuzumab deruxtecan (T-DXd) has shown remarkable intracranial and extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). The DEBBRAH trial was designed to evaluate its efficacy and safety in patients with HER2-positive and HER2-low ABC with a history of brain metastases (BMs) and/or LMD. Here, we report results from cohort 5, which specifically included patients with pathologically confirmed LMD.</p><p><strong>Methods: </strong>This single-arm, open-label, five-cohort, phase 2 trial enrolled seven patients in cohort 5 who received 5.4 mg/kg T-DXd intravenously every 21 days until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) and safety profile.</p><p><strong>Findings: </strong>At data cutoff (April 4, 2023), the median duration of follow-up was 12.0 months (range, 2.5-18.6). The median OS was 13.3 months (95% confidence interval [CI], 5.7-NA, p < 0.001), meeting the primary endpoint. The median PFS was 8.9 months (95% CI, 2.1-NA). Two (28.6%) of seven patients remained on treatment after 18.6 and 11.9 months, respectively. Of the five patients who progressed and died, none had intracranial progression or clinical worsening of leptomeningeal symptoms. Notably, 71.4% (95% CI, 29.0-96.3) achieved prolonged stabilization (≥24 weeks) by response evaluation criteria in solid tumors (RECIST) v.1.1. No unexpected safety signals and no treatment-related deaths were observed.</p><p><strong>Conclusions: </strong>T-DXd showed promising antitumor activity in patients with HER2-positive and HER2-low ABC with previously untreated, pathologically confirmed LMD. These encouraging data warrant further investigation to address the unmet need in this difficult-to-treat condition.</p><p><strong>Funding: </strong>This work was funded by Daiichi Sankyo/AstraZeneca. This trial is registered with ClinicalTrials.gov: NCT04420598.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale pretrained frame generative model enables real-time low-dose DSA imaging: An AI system development and multi-center validation study.","authors":"Huangxuan Zhao, Ziyang Xu, Lei Chen, Linxia Wu, Ziwei Cui, Jinqiang Ma, Tao Sun, Yu Lei, Nan Wang, Hongyao Hu, Yiqing Tan, Wei Lu, Wenzhong Yang, Kaibing Liao, Gaojun Teng, Xiaoyun Liang, Yi Li, Congcong Feng, Tong Nie, Xiaoyu Han, Dongqiao Xiang, Charles B L M Majoie, Wim H van Zwam, Aad van der Lugt, P Matthijs van der Sluijs, Theo van Walsum, Yun Feng, Guoli Liu, Yan Huang, Wenyu Liu, Xuefeng Kan, Ruisheng Su, Weihua Zhang, Xinggang Wang, Chuansheng Zheng","doi":"10.1016/j.medj.2024.07.025","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.025","url":null,"abstract":"<p><strong>Background: </strong>Digital subtraction angiography (DSA) devices are commonly used in numerous interventional procedures across various parts of the body, necessitating multiple scans per procedure, which results in significant radiation exposure for both doctors and patients. Inspired by generative artificial intelligence techniques, this study proposes GenDSA, a large-scale pretrained multi-frame generative model-based real-time and low-dose DSA imaging system.</p><p><strong>Methods: </strong>GenDSA was developed to generate 1-, 2-, and 3-frame sequences following each real frame. A large-scale dataset comprising ∼3 million DSA images from 27,117 patients across 10 hospitals was constructed to pretrain, fine-tune, and validate GenDSA. Two other datasets from 25 hospitals were used for evaluation. Objective evaluations included SSIM and PSNR. Five interventional radiologists independently assessed the quality of the generated frames using the Likert scale and visual Turing test. Scoring consistency among the radiologists was measured using the Kendall coefficient of concordance (W). The Fleiss' kappa values were used for inter-rater agreement analysis for visual Turing tests.</p><p><strong>Findings: </strong>Using only one-third of the clinical radiation dose, videos generated by GenDSA were perfectly consistent with real videos. Objective evaluations demonstrated that GenDSA's performance (PSNR = 36.83, SSIM = 0.911, generation time = 0.07 s/frame) surpassed state-of-the-art algorithms. Subjective ratings and statistical results from five doctors indicated no significant difference between real and generated videos. Furthermore, the generated videos were comparable to real videos in overall quality (4.905 vs. 4.935) and lesion assessment (4.825 vs. 4.860).</p><p><strong>Conclusions: </strong>With clear clinical and translational values, the developed GenDSA can significantly reduce radiation damage to both doctors and patients during DSA-guided procedures.</p><p><strong>Funding: </strong>This study was supported by the National Key R&D Program and the National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes.","authors":"Jieli Lu, Ruixin Liu, Huahui Ren, Shuangyuan Wang, Chunyan Hu, Zhun Shi, Mian Li, Wei Liu, Qin Wan, Qing Su, Qifu Li, Hongting Zheng, Shen Qu, Fangming Yang, Hongyi Ji, Hong Lin, Hongyan Qi, Xueyan Wu, Kui Wu, Yuhong Chen, Yu Xu, Min Xu, Tiange Wang, Jie Zheng, Guang Ning, Ruizhi Zheng, Yufang Bi, Huanzi Zhong, Weiqing Wang","doi":"10.1016/j.medj.2024.07.024","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.024","url":null,"abstract":"<p><strong>Background: </strong>Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear.</p><p><strong>Methods: </strong>We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables.</p><p><strong>Findings: </strong>The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: -1.51 [-2.01, -1.01] mmol/L) compared to the corn oil group (-0.66 [-1.15, -0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation.</p><p><strong>Conclusions: </strong>Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO.</p><p><strong>Funding: </strong>This study was funded by the National Nature Science Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc for GNAO1 encephalopathy: Preclinical profiling and a clinical case.","authors":"Yonika A Larasati, Moritz Thiel, Alexey Koval, Denis N Silachev, Anne Koy, Vladimir L Katanaev","doi":"10.1016/j.medj.2024.07.023","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.023","url":null,"abstract":"<p><strong>Background: </strong>De novo pathogenic variants in GNAO1-the gene encoding the major neuronal G protein Gαo-cause pediatric encephalopathies and other neurological deficiencies largely refractory to available therapies. Zn²⁺ emerged to restore guanosine triphosphate hydrolysis and cellular interactions of pathogenic Gαo; dietary zinc salt supplementation improves lifespan and motoric function in a Drosophila disease model.</p><p><strong>Methods: </strong>Using biochemical, animal, and first-in-human studies, we provide support for the patient stratification and application of zinc acetate in GNAO1-associated disorders.</p><p><strong>Findings: </strong>We show that 16 different pathogenic missense variants cluster in three distinct groups in their responsiveness to Zn²⁺, and we provide the safety study in a mouse disease model. We further describe treatment of a 3-year-old patient with the common pathogenic GNAO1 variant c607G>A, p.Gly203Arg with oral 50 mg zinc (in the form of zinc acetate) daily, as applied in Wilson's disease. During 11 months of treatment, the patient shows cessation of daily dyskinetic crises, improved Burke-Fahn Marsden Dystonia Rating Scale movement score, reduction in epileptic seizures, and an excellent safety profile.</p><p><strong>Conclusions: </strong>Our findings warrant a large-scale clinical trial and might set the new standard of care for GNAO1-related disorders.</p><p><strong>Funding: </strong>This work was funded by the Russian Science Foundation (grant #21-15-00138) and GNAO1 España.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}