European Journal of Pharmaceutical Sciences最新文献

{"title":"NDMA in macrolides: GC-MS/MS method for its detection and study of its formation","authors":"Nejc Golob ,&nbsp;Rok Grahek ,&nbsp;Robert Roškar","doi":"10.1016/j.ejps.2025.107135","DOIUrl":"10.1016/j.ejps.2025.107135","url":null,"abstract":"<div><div><em>N</em>-nitrosodimethylamine (NDMA) is the most commonly found <em>N</em>-nitrosamine in pharmaceutical drug substances (DSs) and drug products. This paper investigates the potential of macrolide antibiotics, containing dimethylamino group, as precursors for NDMA formation in pharmaceuticals. A direct injection GC–MS/MS method was qualified for the quantification of NDMA in various macrolide DSs and film-coated tablets, and the use of pyrrolidine as a scavenger was further emphasized. As an alternative method, GC–MS/MS method with solid phase microextraction was tested, which proved to be unsuitable due to the limited water solubility of macrolides. However, its applicability was confirmed for the analysis of NDMA in water-soluble DSs, such as metformin. The observations regarding the solubility can be applied to a wide range of drug products and analytical methods for the accurate determination of nitrosamines. Various macrolide DSs showed significant levels of NDMA, confirming macrolides as NDMA precursors. In macrolide film-coated tablets, NDMA traces of up to about 70 ppb and 165 ppb were found in azithromycin and spiramycin, respectively, greatly exceeding the acceptable intake limit for NDMA. These findings confirmed the potential of macrolides for NDMA formation which was further enhanced in spiramycin that contains two dimethylamino groups. Furthermore, it has been shown that a stable DS form can successfully prevent NDMA formation, as observed with azithromycin dihydrate. The NDMA content in macrolides can also increase significantly during storage as shown in an accelerated stability study, which together with the levels above the AI limits highlights the need for greater attention and consideration.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107135"},"PeriodicalIF":4.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting bacterial and human levodopa decarboxylases for improved drug treatment of Parkinson's disease: Discovery and characterization of new inhibitors","authors":"Saku Reunanen ,&nbsp;Leo Ghemtio ,&nbsp;Jayendra Z. Patel ,&nbsp;Darshit R. Patel ,&nbsp;Kerttu Airavaara ,&nbsp;Jari Yli-Kauhaluoma ,&nbsp;Michael Jeltsch ,&nbsp;Henri Xhaard ,&nbsp;Petteri T. Piepponen ,&nbsp;Päivi Tammela","doi":"10.1016/j.ejps.2025.107133","DOIUrl":"10.1016/j.ejps.2025.107133","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a common neurodegenerative disease, typically treated with levodopa, which alleviates the motor symptoms of the disease. However, levodopa metabolism in peripheral tissues hampers its bioavailability and leads to undesired side-effects. Therefore, co-administration of amino acid decarboxylase (AADC) inhibitors is necessary, but still, up to 50 % of levodopa may not reach the brain. Recent evidence suggests that gut microbes, especially <em>Enterococcus faecalis</em>, are also able to metabolize levodopa and affect the bioavailability by utilizing microbial tyrosine decarboxylase (TyrDC) enzyme. The main aim of this study was to develop inhibitors targeting gut microbial and host decarboxylation of levodopa. First, a virtual screen of a library of 158,000 compounds against <em>E. faecalis</em> TyrDC was conducted, combining three methods: molecular docking against the <em>E. faecalis</em> TyrDC homology model, structure-based pharmacophore model, and shape similarity searches based on levodopa, carbidopa (AADC inhibitor) and (<em>S</em>)-<em>α</em>-fluoromethyltyrosine (TyrDC inhibitor). A total of 394 compounds were selected and tested <em>in vitro</em> by using a cell-based <em>E. faecalis</em> assay measuring inhibition of levodopa metabolism. Three most active compounds (49-92% inhibition at 100 µM) sharing a similar scaffold and a set of commercially available and in-house synthesized analogs were then assessed against purified TyrDC and AADC enzymes. The IC₅₀ values for the most potent compounds for TyrDC and AADC inhibition were 23 µM / 102 µM (compound <strong>1</strong>), 42 µM / 154 µM (compound <strong>2</strong>) and 51 µM / 182 µM (compound <strong>3</strong>), respectively. These compounds also displayed cytotoxic effects on HeLa cells and modest antibacterial activity against <em>E. faecalis</em> at the same concentration range. The core structure of the compounds presented here can serve as a starting point for the development of a new inhibitor class against TyrDC and AADC, and offers a promising avenue for personalized PD treatment, particularly for patients with high levels of gut microbes expressing the levodopa metabolizing TyrDC enzyme.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107133"},"PeriodicalIF":4.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Honoring Prof. Gerhard Winter with the LMU Winter-Workshop special issue.","authors":"Olivia M Merkel, Hristo L Svilenov, Wolfgang Frieß","doi":"10.1016/j.ejps.2025.107131","DOIUrl":"10.1016/j.ejps.2025.107131","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107131"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional enzyme delivery via surface-modified mesoporous silica nanoparticles in 3D printed nanocomposite hydrogels","authors":"Alaa Mahran ,&nbsp;Fadak Howaili ,&nbsp;Rajendra Bhadane ,&nbsp;Rathna Mathiyalagan ,&nbsp;Tapani Viitala ,&nbsp;Xiaoju Wang ,&nbsp;Jessica M. Rosenholm","doi":"10.1016/j.ejps.2025.107132","DOIUrl":"10.1016/j.ejps.2025.107132","url":null,"abstract":"<div><div>Three-dimensional (3D) printed hydrogel-based scaffolds have emerged as promising for the delivery of biologicals. Recently, we developed a printable plant-based nanocomposite hydrogel, composed of anionic cellulose nanofibers (T-CNF) and methacrylated galactoglucomannan (GGMMA), reinforced with mesoporous silica nanoparticles (MSNs) of different surface charges. However, ensuring the biological activity of the delivered biomolecules requires further investigation to validate the functionality of the developed biomaterial. To investigate this, in this study, horseradish peroxidase (HRP) and lysozyme were selected as distinct model proteins, assessing their immobilization stability and biological activity after MSN immobilization and 3D printing. The interactions between the enzymes and differently surface-modified MSNs were explored using multi-parametric surface plasmon resonance (MP-SPR) and molecular dynamics (MD) simulations. We observed that MSN surface charge is key to the extent of enzyme adsorption and activity control. Positively charged MSNs showed the highest HRP immobilization but caused significant activity loss in both enzymes. In contrast, near-neutral and negatively charged MSNs provided improved stability and activity retention for HRP and lysozyme, respectively. Except for lysozyme/hydrogel, HRP/hydrogel and enzyme-loaded nanocomposite hydrogels (HRP-loaded near-neutral and lysozyme-loaded negatively charged MSNs) were successfully 3D printed using different UV post-curing times. While enzyme-laden nanocomposite scaffolds showed promising immobilization stability, the presence of the photoinitiator caused significant inactivation for both enzymes. Irrespective of the crosslinking approach, this matrix demonstrates significant potential as a delivery carrier for various biomolecules, with promising applications in tissue engineering and wound healing.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107132"},"PeriodicalIF":4.3,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining high-throughput ASD screening with the rDCS to streamline development of poorly soluble drugs","authors":"Malte Bøgh Senniksen ,&nbsp;Nicole Wyttenbach ,&nbsp;Susanne Page ,&nbsp;Jennifer Dressman","doi":"10.1016/j.ejps.2025.107130","DOIUrl":"10.1016/j.ejps.2025.107130","url":null,"abstract":"<div><div>Poor aqueous solubility and slow dissolution rate of active pharmaceutical ingredients (APIs) are often encountered challenges during oral drug development, leading to variable and insufficient bioavailability. To overcome these challenges, a so-called “enabling” formulation strategy is often pursued. Among these, amorphous solid dispersions (ASDs) are established as an effective means of improving drug absorption. However, evaluating the outcome of in vitro ASD screening approaches and relating this to the expected bioavailability increase can be difficult if not done systematically. Here we show, for the first time, how the combination of a high-throughput ASD screening method with the refined Developability Classification System (rDCS) can streamline the formulation of poorly soluble APIs as ASDs. Using the Screening of Polymers for Amorphous Drug Stabilization (SPADS) approach to rapidly prepare ASD films, the improvement in dissolution performance of three APIs (befetupitant, celecoxib and itraconazole) was investigated with eight polymeric carriers. The results showed that the concentration of dissolved API was highly dependent on both the carrier and the drug load. For the APIs studied, Eudragit E, HPMC 100LV and Soluplus showed especially advantageous effects as carriers. Translating these results into the rDCS framework allowed for the visualization of the left-shift (more favorable for absorption) in classification. Several ASD films were classified as rDCS class I, showing a major improvement from the initial IIb classification of the pure API. This novel approach could be expanded to include a diverse set of screening methods for enabling formulation strategies, where the rDCS can allow for a direct comparison and support formulation selection.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107130"},"PeriodicalIF":4.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Global Bioequivalence Harmonisation Initiative (GBHI): Report of the sixth international EUFEPS/PQRI conference","authors":"B. Schug ,&nbsp;G. Beuerle ,&nbsp;E. Bilensoy ,&nbsp;J. Cook ,&nbsp;E. Fernandes ,&nbsp;S. Haertter ,&nbsp;R. Kuribayashi ,&nbsp;M. Mehta ,&nbsp;P. Paixao ,&nbsp;A. Seidlitz ,&nbsp;N. Tampal ,&nbsp;Y.-C. Tsang ,&nbsp;J. Walstab ,&nbsp;R. Wedemeyer ,&nbsp;J. Welink ,&nbsp;W. Jiang","doi":"10.1016/j.ejps.2025.107129","DOIUrl":"10.1016/j.ejps.2025.107129","url":null,"abstract":"&lt;div&gt;&lt;div&gt;At the 6&lt;sup&gt;th&lt;/sup&gt; International Conference of the Global Bioequivalence Harmonisation Initiative (GBHI), co-organised by the European Federation of Pharmaceutical Sciences (EUFEPS) and the Product Quality Research Institute (PQRI), critical bioequivalence (BE) topics were discussed by pharmaceutical scientists from academia, industry and regulatory agencies, revealing the following main conclusions:&lt;/div&gt;&lt;div&gt;(1) Physiologically based pharmacokinetic/biopharmaceutic modelling (PBPK/PBBM) for solid oral drugs: PBPK/PBBM gains increasing recognition for generic drug development, e.g. waivers of fed studies and drug interaction studies with proton pump inhibitors. However, especially for complex formulations containing low-solubility compounds, more data are needed for modelling-based conclusion regarding BE in fed state.&lt;/div&gt;&lt;div&gt;(2) Narrow therapeutic index drugs: A progress towards harmonisation of BE criteria from US-FDA and EMA speakers was made as there is consensus in the usefulness of applying a mixed scale for BE acceptance range depending on variability, via either fully or partially replicated design. Differences still remain regarding variability comparison and the selection of regulatory constant (0.760 vs. 1.05361). All parties confirmed the importance of controlling type-I error.&lt;/div&gt;&lt;div&gt;(3) Single- vs. multiple-dose studies for BE demonstration of modified-release (MR) products: To circumvent multiple-dose studies, model-informed approaches were discussed based on real-life data, e.g. to simulate steady-state profiles from single-dose data. To reduce the burden in patient trials for long-acting injectables promising modelling approaches were presented, extrapolating from incomplete steady-state scenarios.&lt;/div&gt;&lt;div&gt;(4) BE demonstration for additional dose strengths of solid oral MR products: For multiple-unit dosage forms where strengths differ in number of units only, testing BE of the highest dose was considered sufficient. In addition, there was some consensus that, whenever extrapolation from one strength to the others is not easily established, the “bracket-approach” of the EMA focusing on the intake conditions in the label claim (fasted or fed), can help mitigating risks without adding significant cost and effort.&lt;/div&gt;&lt;div&gt;(5) Partial AUC for BE demonstration: Clinical relevance is key to decide on the relevant PK metrics for BE assessment whenever possible. There was consensus that the BE criteria and evaluation strategy may be best specified in product-specific guidances – preferably with international harmonisation.&lt;/div&gt;&lt;div&gt;(6) BE of orally inhaled drug products (OIDPs): The “weight-of-evidence” approach of US-FDA and the stepwise approach of EMA largely differ. The auditorium was in favour of combining data on &lt;em&gt;in-vitro&lt;/em&gt; characteristics and PK exposure. For prediction of comparable efficacy of two OIDPs, there is good trust in PK exposure data whenever they present concentrations being absorbed vi","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107129"},"PeriodicalIF":4.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 8th International Symposium on Phospholipids in Pharmaceutical Research – An update on current research in phospholipids presented at the biennial symposium of the Phospholipid Research Center Heidelberg","authors":"Simon Drescher ,&nbsp;Alfred Blume","doi":"10.1016/j.ejps.2025.107126","DOIUrl":"10.1016/j.ejps.2025.107126","url":null,"abstract":"<div><div>This <em>Conference Report</em> recaps recent advances in the research on phospholipids and their applications for advanced drug delivery and analytical purposes that have been presented at the <em>“8th International Symposium on Phospholipids in Pharmaceutical Research”</em> of the Phospholipid Research Center (PRC), held from September 09–11, 2024, at the University of Heidelberg, Germany. The PRC is a non-profit organization focused on expanding and sharing scientific and technological knowledge of phospholipids in pharmaceutical and related applications. This is accomplished by<em>, e.g.</em>, funding doctoral and postdoctoral research projects at universities worldwide. The PRC organizes this symposium every two years, at which international experts from science and industry present innovative and new applications of phospholipids. This year’s symposium highlighted advancements in lipid-based gene and RNA delivery, anisotropic lipid nanoparticles, PEGylation challenges, tetraether lipids for drug delivery, ethical considerations in publishing, multifunctional lipopeptides, and phospholipid applications in therapeutics. Discussions also showcased award-winning research on optimizing liposome drug compatibility, reflecting the expanding role of phospholipids in pharmaceutical science.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107126"},"PeriodicalIF":4.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced electrochemical immunosensor utilizing pATA/AuNPs for sensitive detection of the leukemia-associated biomarker CD123 in bone marrow supernatant","authors":"Xin Li ,&nbsp;Qing Wang ,&nbsp;Chun-Rong Qin ,&nbsp;Ai-Lin Liu ,&nbsp;Yong Chen","doi":"10.1016/j.ejps.2025.107124","DOIUrl":"10.1016/j.ejps.2025.107124","url":null,"abstract":"<div><h3>Background</h3><div>Cluster of differentiation 123 (CD123) prominently overexpress in various hematological malignancies and plays a crucial role in diagnosis and prognosis of leukemia. Clinical studies have demonstrated that cell-free CD123 levels also significantly influence leukemia immunotherapy outcomes. The development of novel electrochemical immunosensors addresses the need for point-of-care detection tools, thereby facilitating advancements in clinical monitoring technologies.</div></div><div><h3>Methods</h3><div>This study presented a practical electrochemical immunosensor constructed using sandwich strategy for CD123 detection based on the modification of gold nanoparticles and poly (2-aminoterephthalic acid). Common proteins and tumor-related biomarkers found in human were selected as interference factors to evaluate the detection specificity of the electrochemical immunosensor. Further, the electrochemical immunosensor was utilized to directly detect CD123 in bone marrow supernatant from leukemia patients.</div></div><div><h3>Results</h3><div>The constructed electrochemical immunosensor exhibited good linearity for CD123 detection over a range of 0.02 to 2.5 µg/mL, with a detection limit of 12.8 ng/mL, alongside satisfactory specificity and repeatability. Furthermore, the immunosensor was successfully employed to detect CD123 levels in the bone marrow supernatant of leukemia patients, demonstrating results that were highly consistent with those obtained via ELISA.</div></div><div><h3>Conclusions</h3><div>The developed approach is anticipated to provide robust technical support for the long-term monitoring of leukemia patients during their diagnosis and treatment.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"211 ","pages":"Article 107124"},"PeriodicalIF":4.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can the pH-stat lipolysis model be used to assess the performance of supersaturated lipid-based type I formulations?","authors":"Felix Paulus ,&nbsp;Annette Bauer-Brandl ,&nbsp;Jef Stappaerts ,&nbsp;Martin Brandl ,&nbsp;Rosanth Vasantharasan ,&nbsp;René Holm","doi":"10.1016/j.ejps.2025.107125","DOIUrl":"10.1016/j.ejps.2025.107125","url":null,"abstract":"<div><div>A recent <em>in vivo</em> study investigated the impact of supersaturation, lipid chain length, and lipase- and precipitation inhibition on the oral absorption of cinnarizine from type I Lipid-based formulations (LBFs). The aim of the current work was to investigate these formulations using the pH-stat lipolysis model, a well-established method for <em>in vitro</em> investigation of LBFs. This method allows the determination of the extent of lipolysis and of the drug distribution during lipolysis. The pH-stat experiment revealed that LBFs containing medium-chain triglycerides (MCT) were digested more than those containing long-chain triglycerides (LCT). Notably, digestion decreased by at least 75 % in the presence of the lipase inhibitor orlistat. XRPD measurements indicated the presence of amorphous cinnarizine upon precipitation. No correlation was found between the drug concentration in the aqueous phase (<em>in vitro</em> area under the curve (AUC)) and the <em>in vivo</em> AUC (R² = 0.022). However, when considering the drug concentration in the micellar phases, a stronger correlation was observed (R² = 0.17), which further improved when only considering MCT-based formulations (R² = 0.85). The poor correlation for LCT-based formulations could be attributed to their poor dispersibility in aqueous media. Overall, an acceptable correlation was found for MCT-based supersaturated formulations considering the drug concentration in the micellar phases. For potential improvement in predictability for supersaturated type I LBFs containing LCT, one will need to discuss whether the observed poor dispersibility in aqueous media is an artefact of the current lipolysis workflow.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107125"},"PeriodicalIF":4.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothalamic connectivity strength is decreasing with polygenic risk in migraine without aura patients","authors":"Anna Németh ,&nbsp;Kinga Gecse ,&nbsp;Dóra Török ,&nbsp;Dániel Baksa ,&nbsp;Dóra Dobos ,&nbsp;Csaba Sándor Aranyi ,&nbsp;Miklós Emri ,&nbsp;György Bagdy ,&nbsp;Gabriella Juhász","doi":"10.1016/j.ejps.2025.107123","DOIUrl":"10.1016/j.ejps.2025.107123","url":null,"abstract":"<div><div>Migraine is a heritable primary headache disorder which pathophysiology involves altered hypothalamic activity during migraine attacks. To explore the relationship between hypothalamic functional connectivity (HYPT FC) and genetic predisposition characterised by polygenic risk scores (PRS), in migraine, this research examines two types of PRS: one based on all migraine patients (PRS_ALL) regardless of their time of diagnosis and other disorders, and another on migraine-first patients (PRS_FIRST), whose first diagnosed condition was migraine in their lifetime. In an independent sample of 35 migraine patients and 38 healthy controls, using resting-state functional magnetic resonance (rfMRI, 3T) brain imaging, the study reveals significant hypoconnectivity of hypothalamus with the two investigated PRS scores but with different brain areas. While weakened hypothalamic connections in relations with PRS_ALL highlight regions involved in pain modulation, correlation with PRS_FIRST emphasizes decreased connections with sensory and integrative brain areas, suggesting a link between migraine-first genetic risk and cortical hyperexcitability. Our results demonstrate that the polygenic risk of different migraine subgroups may advance our insight into the specific genetic and neural underpinnings of migraine, advancing precision medicine approaches in this field.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"210 ","pages":"Article 107123"},"PeriodicalIF":4.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}