{"title":"[Current status of MPS studies in domestic and overseas-introduction of cardiac MPS].","authors":"Daiju Yamazaki","doi":"10.1254/fpj.24070","DOIUrl":"10.1254/fpj.24070","url":null,"abstract":"<p><p>MPS is already being utilized in various aspects of drug development. This paper introduces MPS from a different viewpoint in previous reviews. First, I will introduce how the term \"microphysiological systems\" came to be used based on the results of the PubMed search, and show the results of an abstract analysis at the MPS World Summit 2023 held in Berlin, which quantified the organs of interest in MPS and the needs of pharmaceutical companies. Next, the author's activities in the AMED-MPS2 (the identification and experimental validation of device or cell considerations as MPS evaluation systems) and MPS-RS (the development of CoUs suitable for guidelines) projects as MPS projects in Japan will be introduced. I am also engaged in the construction of an evaluation system using cardiac MPS. The features and results of several cardiac MPS devices that have been developed for the contraction evaluation will be introduced, including the author's own efforts. Evaluation systems using MPS are attracting attention not only in drug discovery but also in the food and chemical industries, and while social implementation is gradually advancing, discussion groups are being created around the world to discuss how MPS should truly be utilized in society and in regulations. Countries seem to be focusing on acquiring data using useful devices that have survived the race for survival. For Japan to lead the world, it will be necessary to quickly identify useful devices and acquire enough data to discuss them.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"87-91"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536987","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":"[Aceneuraminic acid for distal myopathy].","authors":"Masashi Aoki","doi":"10.1254/fpj.24090","DOIUrl":"https://doi.org/10.1254/fpj.24090","url":null,"abstract":"<p><p>Distal myopathy with rimmed vacuoles (GNE myopathy) is an incurable disease that develops after the late teens, progresses slowly, and has no effective treatment. It is inherited in an autosomal recessive manner, and the number of patients in Japan is estimated to be around 400. The causative gene was revealed to be GNE, the rate-limiting enzyme in the sialic acid biosynthesis pathway, and non-clinical studies demonstrated the effectiveness of sialic acid. Tohoku University Hospital conducted an investigator-initiated phase I trial with aceneuraminic acid in 2010. After that, trials were conducted overseas, and a phase II trial using acenoiraminic acid sustained-release tablets confirmed that muscle strength in the upper limbs had recovered, and the drug progressed to a phase III trial. In Japan, a Phase II/III study was conducted at five domestic facilities using the same protocol as the overseas Phase III study, and efficacy and safety were confirmed. However, Phase III trials overseas failed to show efficacy and development was discontinued. An additional confirmation study was conducted in Japan, and as a result of confirming reproducibility, the product was approved for manufacturing and sales in March 2024, ahead of the rest of the world. This is a successful example of the development of a therapeutic drug for an ultra-orphan disease, which is said to be difficult to develop, and is expected to lead to early treatment for patients.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 1","pages":"48-52"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931030","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":"[Development of fast dissolving sublingual immunotherapy tablet enhancing medication accessibility].","authors":"Takashi Yamamoto, Hiroki Matsuhara, Katsuyo Ohashi-Doi","doi":"10.1254/fpj.24083","DOIUrl":"https://doi.org/10.1254/fpj.24083","url":null,"abstract":"<p><p>In the overall Japanese population, the prevalence of perennial allergic rhinitis (AR) increased from 18.7% to 24.5% from 1998 to 2019. For Japanese cedar pollen (JCP) induced AR, the prevalence in the same period increased from 16.2% to 38.8% in the general population and from 7.2% to 30.1% in children (5-9 years), indicating a serious problem especially in younger age groups. Allergy immunotherapy (AIT) is an AR treatment modality that induces immune tolerance to allergens by repeated allergen administration and is the only treatment form that reduces symptoms and medication use and provides sustained effect after treatment completion. In Japan, AIT is available primarily as sublingual immunotherapy (SLIT) tablets. Two tablets based on a freeze-dried formulation (a JCP SLIT-tablet, approved 2018, and a house dust mite (HDM) SLIT-tablet, approved 2015), and one tablet based on a compressed formulation (HDM, approved 2015) are available. For SLIT to be effective, the concentration of allergen when solubilized in saliva must be as high as possible for as long as possible within the recommended sublingual holding time (1-2 minutes), parameters that must be supported by the tablet formulation. The characteristics of the freeze-dried and compressed formulations were compared using the HDM SLIT-tablets. Freeze-dried tablets disintegrated immediately and displayed fast and complete HDM allergen release in solvent, while compressed tablets disintegrated more slowly and provided only incomplete allergen release. Freeze-dried SLIT-tablets are believed to provide full mucosal availability of the allergen content during the sublingual holding time, and a low medication burden.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 1","pages":"32-36"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931069","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":"[Causes of taste hyposensitivity in daily life and health risks: including the taste of fatty acids].","authors":"Keiko Yasumatsu, Yumiko Nagai, Fumie Ueshima","doi":"10.1254/fpj.24092","DOIUrl":"10.1254/fpj.24092","url":null,"abstract":"<p><p>The sensory system detects the internal and external environment of the body and the stimulus trigger feedback loops toward the set point to maintain homeostasis, but if taste sensitivity has changed, we may consume more nutrients or loss of appetite. These can lead metabolic syndrome or malnutrition, which can lead to frailty. In this review, we examined which of the five basic tastes (sweet, umami, bitter, sour, and salty) is affected by aging. Next, we summarize the effects of oral bacteria and tongue coating on taste, which can cause problems such as bad breath and aspiration pneumonia. Even healthy people can change their taste sensitivity and pose health risks if they continue to eat certain taste substances on a daily basis. Furthermore, we summarize research from the discovery of the taste of fatty acids to the present, and discuss how the involvement of taste in food intake regulation contributes to homeostasis through a literature survey. Recently, a gut-brain circuit for fat preference has been identified. In the intestine, fatty acids are sensed by the same receptors as those in the taste buds of the tongue, and nutritional information is sent to the brain via the vagus nerve. It is very interesting that nerves that convey fatty acid-specific information have been discovered. In this way, taste system of the tongue and nutrition-sensing in the digestive tract are very similar, so we think it will be very meaningful to progress research by referring to each other.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"73-78"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536969","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":"[Drugs and cellular dynamics in tumor microenvironment using microphysiological systems].","authors":"Yuji Nashimoto","doi":"10.1254/fpj.24063","DOIUrl":"10.1254/fpj.24063","url":null,"abstract":"<p><p>The tumor microenvironment (TME) includes immune cells, cancer-associated fibroblasts (CAFs), endothelial cells, pericytes, and more. Previously, these non-cancer cells were considered inactive components in cancer pathology. However, it has become evident that these cells and their secretions play crucial roles in cancer progression. To unravel the complexity of the TME and elucidate its mechanisms, microphysiological systems (MPS) have gained attention. An MPS is defined as \"a microscale cell culture platform for in vitro modeling of functional features of a specific tissue or organ of human or animal origin\", allowing for the control of the chemical or physical conditions of the TME and the analysis of the responses of cancer cells and surrounding cells. In recent years, the incorporation of vascular networks into tumor MPS has enabled more accurate assessments of the dynamics within the TME. This review provides an overview of the latest research on cancer MPS with vascular networks and the cellular and molecular dynamics within the TME.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"97-101"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536991","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":"[Pharmacological characteristics and clinical effectiveness of Futibatinib (Lytgobi<sub>®</sub> Tablets), a covalently-binding, irreversible FGFR1-4 inhibitor].","authors":"Katsuya Takagaki, Ryota Okude, Naoki Hirayama, Hiroshi Sootome, Hiroshi Hirai","doi":"10.1254/fpj.24045","DOIUrl":"10.1254/fpj.24045","url":null,"abstract":"<p><p>Futibatinib (Lytgobi<sub>®</sub> Tablets 4 mg), a novel fibroblast growth factor receptor (FGFR) inhibitor developed by Taiho Pharmaceutical using the Cysteinomix Drug Discovery Platform, was approved in Japan in June 2023 for the treatment of patients with unresectable biliary tract cancer with FGFR2 fusion or rearrangement that had progressed after at least one prior chemotherapy. Futibatinib covalently binds to the cysteine residue in the FGFR kinase domain P-loop structure and is believed to exert antitumor activity by selectively and irreversibly inhibiting FGFR1-4. Many FGFR inhibitors under development are ATP-competitive; however, futibatinib is the first approved covalently-binding irreversible FGFR inhibitor. It inhibits cell proliferation by inhibiting FGFR phosphorylation and its downstream signaling pathways in cancer cell lines. Futibatinib showed inhibitory activity against a wider range of FGFR mutants than ATP-competitive, reversible FGFR inhibitors and inhibited cell proliferation without significantly deviating from the inhibitory effect on wild-type FGFR. Futibatinib showed antitumor efficacy in mice subcutaneously transplanted with human tumor cell lines driven by FGFR. The international phase 2 study (TAS-120-101) was conducted in patients with refractory intrahepatic cholangiocarcinoma with FGFR2 fusion or rearrangement. The overall response rate was 41.7%, showing consistent efficacy regardless of co-occurring genomic alterations. Although some typical FGFR inhibitor-related side effects were observed, they were manageable and futibatinib had a good safety profile. Futibatinib is an important drug for biliary tract cancer, which has limited treatment options; its development is underway for other types of cancer, and it is expected to benefit more patients.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":" ","pages":"423-432"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389220","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}