Journal of Personalized Medicine最新文献

{"title":"The Immune System and the Plural Autisms: A Narrative Review.","authors":"Paul Whiteley, Kevin Carr, Paul Shattock, Malcolm Hooper, Carol Stott, Karl Hardy, Ben Marlow, Chandoshi Rhea Mukherjee, Athena Whiteley","doi":"10.3390/jpm16070379","DOIUrl":"10.3390/jpm16070379","url":null,"abstract":"<p><p>Plural autisms offer one important way of organising the massive heterogeneity that is currently included under the singular diagnostic label of autism spectrum disorder (ASD). Characterised exclusively by behavioural criteria related to social communication skills and restricted or repetitive patterns of symptoms, the observable diversity in presentations and developmental trajectories partially explains the lack of universally applicable biomarkers and answers about underlying biology. One particularly important area potentially pertinent to several manifestations of the plural autisms is a connection to the immune system, whether noted across differing patterns of immune functions or following immune challenge in the context of inflammatory processes exerting an effect on developmental processes and behaviour. Utilising a narrative review, we highlight various research analysing a role for immune functions in the context of the heterogeneous autisms stretching across under-, over- and autoimmune processes. Current evidence for immune system involvement in various autisms carries considerable limitations, and studies are often based on small sample sizes, focusing on selective clinical subgroups, and using case-based observations. Notwithstanding the available evidence, substantial and more detailed further studies are required in relation to immune-related screening, building also on the currently limited evidence on the potential usefulness of personalised immune-affecting interventions following appropriate screening and identification of pertinent immune-related issues.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Description: A Functional GIUS-Based Algorithm for Enteral Feeding Decisions in the ICU.","authors":"Nick Weidner, Christian von Löffelholz, Robert Patejdl, Jan Seyfferth, Heinrich Volker Groesdonk","doi":"10.3390/jpm16070376","DOIUrl":"10.3390/jpm16070376","url":null,"abstract":"<p><p>Gastrointestinal dysfunction is common in critically ill patients and frequently compromises the delivery and tolerance of enteral nutrition. Traditional bedside markers such as gastric residual volume or nonspecific abdominal symptoms provide only limited diagnostic accuracy and often fail to capture dynamic alterations in gastrointestinal function. Gastrointestinal ultrasound (GIUS) has emerged as a noninvasive, bedside-applicable method that enables structural and functional assessment of the gastrointestinal tract and may support more individualized nutritional management in intensive care. This narrative review summarizes the physiology and pathophysiology of gastric emptying and intestinal transit in critically ill patients, reviews established GIUS protocols, including Gastrointestinal and Urinary Tract Sonography (GUTS), Acute Gastrointestinal Injury Ultrasound Scoring (AGIUS), the Lai protocol, and the Ultrasound Meal Accommodation Test (UMAT), and proposes pragmatic GIUS-based algorithms for enteral feeding decisions. Three clinical use cases are addressed: 8 h monitoring during ongoing enteral nutrition, preprandial assessment of feeding readiness, and once-daily screening of gastrointestinal function. Current evidence supports the clinical relevance of key sonographic parameters such as gastric antral cross-sectional area and small-bowel diameter, whereas other measures, including mucosal thickness, colonic wall thickness, and Doppler-derived resistive indices, require further validation. UMAT adds a dynamic component to static sonographic assessment and may improve the evaluation of gastric accommodation and emptying in selected patients. Structured GIUS protocols offer a promising, evidence-informed extension of bedside assessment for enteral nutrition management in the intensive care unit. However, the available literature remains heterogeneous and is largely based on physiological studies, observational cohorts, and expert consensus. Prospective multicenter studies are needed to validate cutoff values, training standards, and outcome effects before GIUS-based algorithms can be adopted as stand-alone decision tools.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET Enzymes as Epigenetic Integrators in Intestinal Immunity, Inflammation, and Disease.","authors":"Dhirendra K Singh, Yukihiro Yamaguchi, Lei Huang, Chieko Saito, Olivia G Cassidy, Keita Nishiyama","doi":"10.3390/jpm16070375","DOIUrl":"10.3390/jpm16070375","url":null,"abstract":"<p><p>DNA methylation plays a fundamental role in maintaining intestinal homeostasis, immune tolerance, and inflammatory balance. Active DNA demethylation, mediated by the ten-eleven translocation family of dioxygenases (TET1, TET2, and TET3), has emerged as an important epigenetic mechanism linking environmental and metabolic cues to gene regulatory programs in the gut. In the intestinal epithelium, TET-dependent DNA hydroxymethylation contributes to intestinal stem cell maintenance, epithelial differentiation, regeneration, and barrier integrity. Perturbations in TET activity are associated with epithelial dysfunction, chronic inflammation, and increased susceptibility to colorectal tumorigenesis. Within the immune compartment, TET-mediated demethylation is required for the epigenetic stabilization of gut-associated immune cells. Altered TET function has been implicated in immune imbalance in inflammatory bowel disease, Hirschsprung's disease, and colitis-associated colorectal cancer. Emerging evidence further indicates that intestinal microbiota-derived metabolites, including short-chain fatty acids and aryl hydrocarbon receptor ligands, modulate TET activity, positioning TET enzymes as epigenetic sensors of microbial and metabolic signals. In turn, TET-dependent programs shape immune responses to commensal microbes and pathogens, establishing a bidirectional microbiota-epigenetic axis that influences both intestinal and systemic immunity. In this review, we summarize and critically evaluate current evidence on the roles of TET enzymes in intestinal epithelial biology, immune cell regulation, and host-microbiota interactions in colorectal inflammation and disease.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wearable Devices and Machine Learning in Cardiovascular Monitoring: Current Evidence and Future Directions for Precision Medicine.","authors":"Ayokunle Osonuga, Madhavi Dave, Ikponmwosa Jude Ogieuhi, David B Olawade, Stergios Boussios","doi":"10.3390/jpm16070377","DOIUrl":"10.3390/jpm16070377","url":null,"abstract":"<p><p>Cardiovascular disease remains the leading global health challenge, claiming approximately 19.8 million lives annually. The convergence of wearable technology and artificial intelligence represents a transformative shift in cardiovascular healthcare, enabling continuous real-time monitoring beyond conventional clinical settings. This narrative review synthesises current evidence on integrating consumer-grade and medical-grade wearable devices with AI algorithms for continuous cardiovascular monitoring applications, with particular attention to real-world translational applicability and global health equity. This review examined the technological landscape of wearable cardiovascular monitoring devices, including smartwatches with photoplethysmography and electrocardiogram capabilities, continuous cardiac monitoring patches, and emerging biosensor technologies. Also, the review explored AI methodologies, particularly machine learning and deep learning architectures, employed in processing complex physiological data streams from these devices. Clinical applications demonstrate impressive capabilities: arrhythmia detection with sensitivity rates exceeding 98%, continuous blood pressure monitoring through cuffless technologies, heart failure decompensation prediction, and cardiovascular risk stratification. However, substantial challenges persist, including data quality assurance, algorithm interpretability, regulatory compliance, and seamless clinical workflow integration. Privacy concerns, health disparities in algorithm performance, and the need for robust validation across diverse populations remain critical considerations. AI-enhanced wearable systems hold considerable potential for shifting cardiovascular care from reactive treatment paradigms towards predictive, preventive, and precision medicine approaches. Future directions include edge computing architectures, federated learning approaches, personalised AI models, enhanced interoperability with electronic health records, and expansion to resource-limited settings, ultimately improving patient outcomes whilst reducing healthcare costs.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Association to Prediction: Translational Barriers in Pain Biomarker Research.","authors":"Gustavo Fabregat-Cid, Natalia Escrivá-Matoses, José De Andrés","doi":"10.3390/jpm16070374","DOIUrl":"10.3390/jpm16070374","url":null,"abstract":"<p><p>Pain biomarkers have been proposed as potential tools to improve patient stratification, treatment selection, and individualized therapeutic strategies in chronic pain. However, despite an increasing volume of research across neuroimaging, electrophysiological, and molecular domains, their translation into clinical practice remains limited. A central challenge lies in the conceptual and methodological misalignment between biomarker discovery and clinical applicability. Many studies labelled as \"predictive\" rely on measurements obtained during or after intervention, small sample sizes, or lack of external validation, limiting their ability to inform real-world decision-making. In addition, the distinction between predictive, monitoring, and mechanistic biomarkers is often blurred, further complicating interpretation and implementation. This Perspective examines why many candidate pain biomarkers, although biologically informative, have not yet become clinically actionable tools for treatment selection. We distinguish between associative, mechanistic, monitoring, preventive, and truly predictive biomarkers using clinically relevant examples from pain research, and we outline the methodological requirements needed to translate biomarker discovery into precision pain medicine. We argue that the field requires a more rigorous framework for defining and validating predictive biomarkers, encompassing appropriate timing of measurement, robust study design, external validation, and patient-relevant endpoints. Without this framework, pain biomarker research risks continuing to generate biologically informative but clinically non-actionable findings that do not advance individualized therapeutic decision-making.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13413249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Effect and Personalization of Intraoperative Hypotension Burden on Postoperative Acute Kidney Injury: A Doubly Robust Analysis of the VitalDB Cohort.","authors":"Seung-Bo Lee","doi":"10.3390/jpm16070371","DOIUrl":"10.3390/jpm16070371","url":null,"abstract":"<p><p><b>Background</b>: Intraoperative hypotension (IOH) is the leading modifiable contributor to postoperative acute kidney injury (AKI), yet most evidence is associational and the heterogeneity of its effect is unknown. We estimated the causal effect of IOH burden on AKI and tested whether the most susceptible patients can be identified preoperatively. <b>Methods</b>: In a retrospective cohort of 2726 general-anesthesia cases from VitalDB, the exposure was the time-integrated mean arterial pressure (MAP) <65 mmHg burden (≥30, ≥60 and ≥120 mmHg·min) and the outcome was KDIGO-defined AKI within 7 days. The primary estimator was pre-treatment-adjusted augmented inverse-probability weighting (AIPW; doubly robust) with bootstrap 95% confidence intervals (CIs). Sensitivity analyses comprised a controlled-direct-effect model, negative control outcomes, E-values and vasopressor-stratified estimates. Effect heterogeneity was estimated with a causal forest; preoperative gradient-boosted models and decision-curve analysis assessed personalization and clinical utility. <b>Results</b>: AKI occurred in 205 (7.52%) cases. At 60 mmHg·min the AIPW risk difference was +3.00 percentage points (pp; 95% CI +0.84 to +5.26), with a monotonic dose-response (+2.78 to +7.62 pp across thresholds) and E-values rising from 2.08 to 3.44. The effect was concentrated in patients with elevated preoperative creatinine (conditional effect +9.86 pp, more than twice the cohort average). This susceptibility was recoverable from routine preoperative variables alone, with intraoperative waveform features conferring no measurable improvement (ΔAUROC -0.001). For predicting AKI itself, a parsimonious 4-feature preoperative score matched a 27-feature model (AUROC 0.775 vs. 0.768) and provided positive net benefit. <b>Conclusions</b>: Intraoperative hypotension burden shows a dose-dependent association with postoperative AKI that is consistent with a causal effect, concentrated in patients with reduced baseline renal reserve who are identifiable from routine preoperative data without intraoperative waveform infrastructure.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13413355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibular Nonunion: A Systematic Review of Incidence, Diagnosis, and Treatment Outcomes.","authors":"Virginia Cinelli, Federico Moretti, Chiara Comisi, Antonio Mascio, Gloria Assegbede, Vincenzo La Vergata, Giulio Maccauro, Carlo Perisano, Tommaso Greco","doi":"10.3390/jpm16070373","DOIUrl":"10.3390/jpm16070373","url":null,"abstract":"<p><p><b>Background:</b> Fibular nonunion is an uncommon but clinically relevant complication following fractures or surgical procedures, often resulting in persistent pain and functional impairment. Due to its rarity, current evidence remains limited and no standardized treatment guidelines are available. <b>Purpose:</b> To systematically review the literature on fibular nonunion, focusing on clinical presentation, diagnostic approaches, and treatment outcomes. <b>Methods:</b> A systematic review was conducted in accordance with PRISMA guidelines. MEDLINE, Scopus, and Web of Science were searched up to July 2025. Studies including adult patients (≥18 years) with fibular nonunion treated either conservatively or surgically were included. Data regarding demographics, clinical presentation, and treatment outcomes were extracted and analyzed descriptively. <b>Results:</b> Nineteen studies comprising 183 patients were included. The mean patient age was 45.7 years, with a predominance of males (58.4%). The distal third of the fibula was the most frequently involved site (75.9%). The mean time to diagnosis was 28.6 weeks. Surgical treatment was performed in 65.6% of cases, most commonly using open reduction and internal fixation. Among studies reporting union outcomes, favorable radiographic healing rates were observed following surgical treatment. Conservative treatment was primarily reserved for asymptomatic or minimally symptomatic patients. The overall complication rate was low (3.8%), mainly consisting of minor infections and hardware-related issues. <b>Conclusions:</b> Fibular nonunion is an uncommon but clinically significant condition. Available evidence suggests that surgical management may represent the most consistently successful treatment strategy in symptomatic and mechanically unstable cases, while nonoperative treatment may remain appropriate in carefully selected asymptomatic or minimally symptomatic patients. However, the available literature is limited by retrospective study designs, heterogeneous populations, inconsistent outcome reporting, and variable definitions of nonunion, highlighting the need for prospective multicenter studies and standardized treatment protocols.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression and Mood Changes in People with Parkinson's Disease over Time: A 5-Year Follow-Up Study.","authors":"Ángela Solleiro-Vidal, Diego Santos-García, Alfredo Puy Núñez, Teresa de Deus Fonticoba, Pablo Mir, Gracia Pons Pons, Juan García Caldentey, Nuria Caballol, Jorge Hernández Vara, Lydia López Manzanares, Bárbara Vives Pastor, Maria A Ávila Rivera, Isabel González Aramburu, Rocío García-Ramos, Carmen Borrué, Julio Dotor García-Soto, María Álvarez Sauco, Iria Cabo, Guillermo González Ortega, Coppadis Study Group","doi":"10.3390/jpm16070372","DOIUrl":"10.3390/jpm16070372","url":null,"abstract":"<p><p><b>Background and Objective:</b> Depression is frequent in Parkinson's disease (PD), but it is unclear how mood changes and impacts patient's quality of life (QoL) over time. Our objective was to analyze the frequency of depression and mood changes in people with PD (PwP) over 5 years of follow-up, comparing it with a control group, as well as its relationship with the patients' QoL. <b>Patients and Methods:</b> PwP and healthy controls (HC) recruited from the COPPADIS cohort from January/2016 to November/2017 were included in this 5-year follow-up study. Mood was assessed by the Beck Depression Inventory II (BDI-II), and participants were classified as having major depression, minor depression, subthreshold depression, or non-depression at baseline and at 2, 4, and 5 years of follow-up. Correlation analysis and linear regression models were applied. <b>Results:</b> The BDI-II total score increased from 8.1 ± 6.2 at baseline to 10.3 ± 8.1 at the 5-year follow-up visit in PwP (<i>p</i> < 0.0001) but not in HC (from 4.1 ± 5.2 to 4.0 ± 5.7 [<i>p</i> = 0.896]). The prevalence of depression remained around 50-54% in the PwP group and 21-25% in the HC group throughout the follow-up period, but the mood state showed variability for each patient between visits. Patients' QoL was associated with the depressive state throughout the entire follow-up period (<i>p</i> < 0.0001). Worsening QoL, sleep, longer disease duration, and an increase in neuropsychiatric symptoms were identified as independent factors associated with a worsening of mood over time in PwP (N = 348). <b>Conclusions:</b> Mood change over time in PwP is associated with QoL.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevertebral Abscess Revealing a Rare Foreign Body: A Case Report.","authors":"Theresa Mally, Nina Rubicz, Paul Martin Zwittag","doi":"10.3390/jpm16070370","DOIUrl":"10.3390/jpm16070370","url":null,"abstract":"<p><p><b>Background:</b> Migrated foreign bodies in the prevertebral region represent a rare but potentially serious condition. This case underscores the importance of thorough visual and digital intraoperative exploration for successful foreign body retrieval and highlights the potential diagnostic and surgical challenges associated with migrated foreign bodies in the cervical region. <b>Case report:</b> A 77-year-old female patient presented with dysphagia following the intake of an Angiotensin-Converting Enzyme (ACE) inhibitor. Due to hemodynamic instability and laboratory findings that indicated multiple organ failure, a computed tomography (CT) scan was performed, which revealed a left-sided prevertebral abscess with gas collections. Because of persistently elevated and fluctuating inflammatory markers, multiple CT scans were performed, which showed an obliquely oriented, wire-like tubular structure approximately 30 mm in length, 5 mm in width and 1 mm in diameter in the prevertebral region of the previous abscess cavity. Eventually, after three surgical interventions-one transoral and two transcervical approaches-the foreign body could be identified and removed. Afterwards, the patient's inflammatory markers decreased and her dysphagia resolved. <b>Conclusions:</b> This case demonstrates that early diagnosis and timely removal of foreign bodies in the cervical space are essential to prevent complications such as retropharyngeal abscess formation or mediastinitis. A combination of careful clinical examination, endoscopic evaluation, and cross-sectional imaging-particularly CT scan-is crucial for accurate localization. Finally, this report highlights the importance of maintaining a high index of suspicion for migrated foreign bodies in patients presenting with persistent symptoms or unexplained cervical infections following suspected foreign body ingestion.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13413190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Drug Repurposing Screen Identifies Patient-Specific Therapeutic Candidates for Mucopolysaccharidosis Type IIIB.","authors":"Kathleen D McDaniel, Neda Ghousifam, Rodney A Bowling, Catherine Z Chen, Wei Zheng, Zeenat A Shyr","doi":"10.3390/jpm16070369","DOIUrl":"10.3390/jpm16070369","url":null,"abstract":"<p><p><b>Background:</b> Mucopolysaccharidosis type IIIB (MPSIIIB, Sanfilippo syndrome type B) is a rare lysosomal storage disease caused by deficiency of alpha-N-acetylglucosaminidase (NAGLU) enzyme, leading to progressive accumulation of heparan sulfate and severe neurological decline. MPSIIIB's significant genetic heterogeneity presents a major barrier to developing broadly effective treatments and suggests a need for personalized therapeutic strategies. <b>Methods:</b> We established a personalized drug repurposing platform using high-content imaging with lysotracker dye as an indirect functional readout of lysosomal dysfunction to screen compounds that correct lysosomal defects in patient-derived fibroblasts. We screened 2807 compounds on cells from an MPSIIIB patient with a homozygous NAGLU p.Arg297Ter mutation. Hits that reduced lysosomal accumulation by at least 25% with minimal cytotoxicity were validated and subsequently tested for efficacy in fibroblasts from a second patient with a different, compound heterozygous NAGLU genotype. <b>Results:</b> The primary screen yielded 72 hits (2.6% hit rate), with 10 confirmed in dose-response assays. Notably, four clinically approved drugs-baclofen, dextrose, epalrestat and moxifloxacin-reduced lysosomal accumulation in the index patient's cells. However, none of these four drugs were effective in the second patient's cells, demonstrating a profound patient-specific effect. Only one non-clinical compound, 6-chlorothymol, showed a trend toward activity in both cell lines. <b>Conclusions:</b> Our study demonstrates a feasible framework for conducting rapid, N-of-1 drug repurposing screens for rare diseases. While we identified four promising candidates for the index patient, the lack of efficacy in a second patient cell line underscores that genetic heterogeneity may preclude a \"one-size-fits-all\" approach for MPSIIIB. These findings support the integration of individualized drug screening as a potential precision-medicine strategy, offering a potential path toward patient-specific therapies for rare diseases rather than traditional drug development.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}