The live biotherapeutic Blautia stercoris MRx0006 attenuates social deficits, repetitive behaviour, and anxiety-like behaviour in a mouse model relevant to autism

Article

作者: Moloney, Gerard M ; Sherwin, Eoin ; Chetal, Sasha ; Fitzgerald, Patrick ; Savignac, Helene ; Schellekens, Harriet ; Olavarría-Ramírez, Loreto ; Sen, Paromita ; Druelle, Clementine ; Rea, Kieran ; Bastiaanssen, Thomaz F S ; Chruścicka-Smaga, Barbara ; Jeffery, Ian B ; Golubeva, Anna ; Mulder, Imke ; Jayaprakash, Pooja ; Campos, David ; Paula Ventura Da Silva, Ana ; Cryan, John F ; Sandhu, Kiran ; Dinan, Timothy G

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and gastrointestinal symptoms. The aetiology of ASD is complex and involves an interplay of genetic and environmental factors. Emerging pre-clinical and clinical studies have documented a potential role for the gut microbiome in ASD, and consequently, the microbiota represents a potential target in the development of novel therapeutics for this neurodevelopmental disorder. In this study, we investigate the efficacy of the live biotherapeutic strain, Blautia stercoris MRx0006, in attenuating some of the behavioural deficits in the autism-relevant, genetic mouse model, BTBR T+ Itpr3tf/J (BTBR). We demonstrate that daily oral administration with MRx0006 attenuates social deficits while also decreasing repetitive and anxiety-like behaviour. MRx0006 administration increases the gene expression of oxytocin and its receptor in hypothalamic cells in vitro and increases the expression of hypothalamic arginine vasopressin and oxytocin mRNA in BTBR mice. Additionally at the microbiome level, we observed that MRx0006 administration decreases the abundance of Alistipes putredinis, and modulates the faecal microbial metabolite profile. This alteration in the metabolite profile possibly underlies the observed increase in expression of oxytocin, arginine vasopressin and its receptors, and the consequent improvements in behavioural outcomes. Taken together, these findings suggest that the live biotherapeutic MRx0006 may represent a viable and efficacious treatment option for the management of physiological and behavioural deficits associated with ASD.

项与 MRx0006 相关的新闻（医药）

2022-07-26

·PRNewswire

New Therapeutics Options in Rheumatoid Arthritis Pipeline as 120+ Key Companies are Working on Drug Profiles | DelveInsight

Rise in prevalence of rheumatoid arthritis, increase in demand for rheumatoid arthritis drugs, the entry of biosimilar drugs, the surge in geriatric population are the key factors driving the development of potential treatment of Rheumatoid arthritis. Major key players include Taisho Pharmaceutical, Zhejiang Hisun Pharmaceutical, SinoMab, Jiangsu Hengrui Medicine, RemeGen, GlaxoSmithKline, Modern Biosciences, Jiangsu Alphamab Biopharmaceuticals, and others. LAS VEGAS, July 26, 2022 /PRNewswire/ -- DelveInsight's ' Rheumatoid Arthritis Pipeline Insight 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline rheumatoid arthritis therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the rheumatoid arthritis pipeline domain. Key Takeaways from the Rheumatoid Arthritis Pipeline Report DelveInsight's rheumatoid arthritis pipeline report depicts a robust space with 120+ active players working to develop 120 + pipeline therapies for rheumatoid arthritis treatment. Key rheumatoid arthritis companies such as Taisho Pharmaceutical, Zhejiang Hisun Pharmaceutical, SinoMab, Jiangsu Hengrui Medicine, RemeGen, GlaxoSmithKline, Modern Biosciences, Jiangsu Alphamab Biopharmaceuticals, Akros Pharma, Hanlim Pharm, Galapagos NV, Chong Kun Dang Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Aclaris Therapeutics, Abivax, AbbVie, Synact Pharma, Gilead sciences, Mesoblast, Rottapharm Biotech, Eli Lilly and Company, Kiniksa Pharmaceuticals, Abcentra, Cyxone, Yungjin Pharm. Co., Ltd. Taiho Pharmaceutical, Oscotec Inc., Pfizer, Janssen Research & Development, Cipher Pharmaceuticals Inc., KLUS Pharma Inc., Revolo Biotherapeutics, Lynk Pharmaceuticals, Beijing Baylx Biotech, Hope Biosciences, Kangstem Biotech, Celltex Therapeutics, I-Mab Biopharma Co. Ltd., Synermore Biologics Co., Ltd, Oryn Therapeutics, Arthrogen, Bayer, Amgen, Draconis Pharma, Biozeus, Landos Biopharma, Imcyse, Kymera Therapeutics, RedHill Biopharma, 4D Pharma, CV6 Therapeutics, VYNE Therapeutics, MyMD Pharmaceuticals, Brickell Biotech Inc, Worg Pharmaceuticals, Almirall, Standigm, Metrion Biosciences, Jnana Therapeutics, Silo Pharma, SFA Therapeutics, Neutrolis Therapeutics, Ahead Therapeutics, Fresenius Kabi, Kidswell Bio, BioXpress Therapeutics, CinnaGen, Alvotech, Hetero Biopharma, Shanghai Henlius Biotech, Cadila Pharmaceuticals, Innovent Biologics, Torrent Pharmaceuticals, Emcure Pharmaceuticals, mAbxience, Shanghai Junshi Biosciences, Enosi Therapeutics, and others are evaluating novel rheumatoid arthritis treatment drugs candidate to improve the treatment landscape. Promising rheumatoid arthritis pipeline therapies in various stages of development includes TS152, HS-016, SM03, SHR0302, RC18, Otilimab, NI-0101, MBS2320, KN019, JTE-051, Interleukin 2, HL237, GLPG3970, Elsubrutinib, CKD-506, Branebrutinib, AZD9567, ATI-450, ABX464, ABBV 3373, ABBV 154, AP1189, F8IL10, AMT-101, GS-9876, CR 6086, LY 3462817, KPL-404, Orticumab, Rabeximod, YRA 1909, VIB4920, Varicella Zoster Vaccine, TAS5315, SKI-O-703, SAN-300, PF-06650833, Nipocalimab, CF-101, A223, IRL 201805, LNK 01001, PRTX-100, hUC-MSC infusion, HB-adMSC, LABP-104, VAY736, TJ003234 , SYN060, GS-5718, PF-06835375, Nivolumab, MH004, ORTD-1, ART-I02, FB704A, Amilo 5MER, CKD-374 , CFZ-533, BAY 1830839, AMG 570, JNJ-4703, CT-P47, BZ068, Invossa, LABP-69, ICM-203-R, NX-5948, KT-474 , Clarithromycin/clofazimine/rifabutin (RHB-104), Research programme: small molecule TYK2 inhibitors, MRx0006, CV6 1271, VYN201, MYMD-1, BBI 02, Research Programme: Immune mediated diseases, Foralumab, SPU-21, SFA002, NTR-441, Research programme: autoimmune disease therapeutics, AT_1001, MSB11456, MabionCD20, DMB-3113, GB232, GBS 005, TX17, BX 2922, Cinnora, AVT02, MYL-1401A, and others. In July 2022, Enosi Therapeutics, announced a partnership with Danuo Science Group, based in Hong Kong, to further develop two products currently in Enosi's pipeline for Greater China. Enosi's Growth Factor Trap (EN-2000 Program) and TNFR1 Blocker (EN-1000 Program) were licensed as part of the partnership. Both programs have the potential to be used as cross-over drugs to treat cancer and autoimmune diseases. EN-2000 blocks inflammatory growth factors that drive cancer and rheumatoid arthritis while EN-1000 is a specific blocker of TNFR1, which Enosi believes may be useful in treating autoimmune disease. In February 2022, Biogen Inc. and Xbrane Biopharma AB announced that they have entered into a commercialization and license agreement to develop, manufacture, and commercialize Xcimzane™, a preclinical monoclonal antibody that is a proposed biosimilar referencing CIMZIA® (certolizumab pegol). In June 2022, Biogen Inc. and Bio-Thera Solutions, Ltd. presented positive Phase III data for BIIB800 (BAT1806), a biosimilar candidate referencing. The double-blind 52-week Phase III study randomized 621 patients with moderate to severe rheumatoid arthritis to receive either BIIB800 or the reference tocilizumab administered intravenously every 4 weeks at a dose of 8 mg/kg for the first 24 weeks. Data from the Phase III comparative clinical trial demonstrated that the investigational biosimilar candidate BIIB800 has equivalent efficacy and comparable safety and immunogenicity profile to the reference tocilizumab product. In June 2022, Revolo Biotherapeutics announced that it was awarded an Innovative Medicines Designation, or Innovation Passport, from the Medicines and Healthcare products Regulatory Agency (MHRA) for its immune-resetting drug candidate, '1805, for the treatment of patients with moderately to severely active Rheumatoid Arthritis (RA). In February 2022, Revolo Biotherapeutics secured approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to initiate two Phase II trials of its autoimmune disease drug candidate '1805. One of the trials will enrol moderate-to-severe active rheumatoid arthritis (RA) patients while another Phase II trial will have individuals with non-infectious, active, intermediate, or posterior uveitis or panuveitis. In December 2021, Theramex, entered into an agreement with Enzene Biosciences Limited to develop, register, and commercialize a biosimilar drug of Roche's reference medicine RoActemra (Tocilizumab). Tocilizumab, in combination with Methotrexate (MTX), is indicated for the treatment of rheumatoid arthritis. It is planned to be commercialized from 2026 in Europe, the UK, Switzerland, and Australia. Obefazimod is an oral, first-in-class, small molecule being developed by Abivax in Phase II stage of development. Obefazimod generated promising pre-clinical data from collagen-induced arthritis animal models that were the basis for moving into the Phase IIa clinical trial in rheumatoid arthritis (RA). Zunsemetinib, an Investigational Oral MK2 Inhibitor, is being developed by Aclaris Therapeutics. Aclaris initiated study activities and began activating sites in December 2021 in the following two studies: ATI-450-RA-202: Phase IIb clinical trial of zunsemetinib in subjects with moderate to severe rheumatoid arthritis (RA). This is Aclaris' second Phase II clinical trial of zunsemetinib in subjects with moderate to severe RA and is primarily designed to assess the efficacy of multiple doses of zunsemetinib to aid in the selection of an optimal dose to progress in future development. Request a sample and discover the recent advances in rheumatoid arthritis treatment @ Rheumatoid Arthritis Pipeline Outlook The rheumatoid arthritis pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage rheumatoid arthritis products, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the rheumatoid arthritis pipeline landscape. Rheumatoid Arthritis Overview Rheumatoid arthritis is classified as an autoimmune disorder. It occurs when the immune system, which is supposed to defend, malfunctions and begins to attack our own tissues. It causes inflammation in the lining of the joints (the synovium). As a result, joints may become red, warm, swollen, and painful, which are common rheumatoid arthritis symptoms. The exact rheumatoid arthritis causes are still unknown. Rheumatoid arthritis can be difficult to detect in its early stages since the early signs and symptoms are similar to those of many other diseases. There is no single blood test or physical finding that can validate the rheumatoid arthritis diagnosis. Rheumatoid arthritis has no known cure. However, rheumatoid arthritis clinical trials show that remission of symptoms is more frequent when rheumatoid arthritis treatment with disease-modifying antirheumatic medicines started early (DMARDs). Find out more about rheumatoid arthritis treatment @ Rheumatoid Arthritis Treatment Drugs A snapshot of the Rheumatoid Arthritis Pipeline Drugs mentioned in the report: Learn more about the novel and emerging rheumatoid arthritis pipeline therapies @ Rheumatoid Arthritis Clinical Trials Rheumatoid Arthritis Therapeutics Assessment The rheumatoid arthritis pipeline report proffers an integral view of rheumatoid arthritis emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Rheumatoid Arthritis Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-ocular, Intra-articular, Intrathecal, Intravenous, Oral, Parenteral, Ophthalmic, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Interleukin 6 inhibitor, Tumour necrosis factor-alpha inhibitor, CD22 antigen inhibitor, Janus kinase 1 inhibitor, B cell activating factor inhibitor, Granulocyte-macrophage colony-stimulating factor antagonist, Toll-like receptor 4 antagonist, Emt protein-tyrosine kinase inhibitor, Fibroblast growth factor modulators; T lymphocyte inhibitors, Bacteria replacements. Key Rheumatoid Arthritis Companies: Taisho Pharmaceutical, Zhejiang Hisun Pharmaceutical, SinoMab, Jiangsu Hengrui Medicine, RemeGen, GlaxoSmithKline, Modern Biosciences, Jiangsu Alphamab Biopharmaceuticals, Akros Pharma, Hanlim Pharm, Galapagos NV, Chong Kun Dang Pharmaceutical, Bristol Myers Squibb, AstraZeneca, Aclaris Therapeutics, Abivax, AbbVie, Synact Pharma, Gilead sciences, Mesoblast, Rottapharm Biotech, Eli Lilly and Company, Kiniksa Pharmaceuticals, Abcentra, Cyxone, Yungjin Pharm. Co., Ltd. Taiho Pharmaceutical, Oscotec Inc., Pfizer, Janssen Research & Development, Cipher Pharmaceuticals Inc., KLUS Pharma Inc., Revolo Biotherapeutics, Lynk Pharmaceuticals, Beijing Baylx Biotech, Hope Biosciences, Kangstem Biotech, Celltex Therapeutics, I-Mab Biopharma Co. Ltd., Synermore Biologics Co., Ltd, Oryn Therapeutics, Arthrogen, Amgen, Biozeus, Landos Biopharma, Imcyse, Kymera Therapeutics, RedHill Biopharma, 4D Pharma, CV6 Therapeutics, VYNE Therapeutics, MyMD Pharmaceuticals, Brickell Biotech Inc, Worg Pharmaceuticals, Almirall, Standigm, Metrion Biosciences, Jnana Therapeutics, Silo Pharma, SFA Therapeutics, Neutrolis Therapeutics, Ahead Therapeutics, Fresenius Kabi, Kidswell Bio, BioXpress Therapeutics, CinnaGen, Alvotech, Hetero Biopharma, Shanghai Henlius Biotech, Cadila Pharmaceuticals, Innovent Biologics, Torrent Pharmaceuticals, Emcure Pharmaceuticals, mAbxience, Shanghai Junshi Biosciences, Enosi Therapeutics, and others Key Rheumatoid Arthritis Pipeline Therapies: TS152, HS-016, SM03, SHR0302, RC18, Otilimab, NI-0101, MBS2320, KN019, JTE-051, Interleukin 2, HL237, GLPG3970, Elsubrutinib, CKD-506, Branebrutinib, AZD9567, ATI-450, ABX464, ABBV 3373, ABBV 154, AP1189, F8IL10, AMT-101, GS-9876, CR 6086, LY 3462817, KPL-404, Orticumab, Rabeximod, YRA 1909, VIB4920, Varicella Zoster Vaccine, TAS5315, SKI-O-703, SAN-300, PF-06650833, Nipocalimab, CF-101, A223, IRL 201805, LNK 01001, PRTX-100, hUC-MSC infusion, HB-adMSC, LABP-104, VAY736, TJ003234 , SYN060, GS-5718, PF-06835375, Nivolumab, MH004, ORTD-1, ART-I02, FB704A, Amilo 5MER, CKD-374 , CFZ-533, BAY 1830839, AMG 570, JNJ-4703, CT-P47, BZ068, Invossa, LABP-69, ICM-203-R, NX-5948, KT-474 , Clarithromycin/clofazimine/rifabutin (RHB-104), Research programme: small molecule TYK2 inhibitors, MRx0006, CV6 1271, VYN201, MYMD-1, BBI 02, Research Programme: Immune mediated diseases, Foralumab, SPU-21, SFA002, NTR-441, Research programme: autoimmune disease therapeutics, AT_1001, MSB11456, MabionCD20, DMB-3113, GB232, GBS 005, TX17, BX 2922, Cinnora, AVT02, MYL-1401A, and others. Dive deep into rich insights for drugs for rheumatoid arthritis, visit @ Rheumatoid Arthritis Medications Table of Contents For further information on the rheumatoid arthritis pipeline therapeutics, reach out @ Drugs for Rheumatoid Arthritis Related Reports Rheumatoid Arthritis Market Rheumatoid Arthritis Market Insights, Epidemiology, and Market Forecast-2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key rheumatoid arthritis companies including Abivax, UCB, Sierra Oncology, Taisho, among others. Rheumatoid Arthritis Epidemiology Forecast Rheumatoid Arthritis Epidemiology Forecast to 2032 report delivers an in-depth understanding of the disease, historical and forecasted rheumatoid arthritis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Juvenile Rheumatoid Arthritis Pipeline Juvenile Rheumatoid Arthritis Pipeline Insight, 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products and the key juvenile rheumatoid arthritis companies, including Novartis, AbbVie, Eli Lilly and Company, Sanofi, among others. Juvenile Rheumatoid Arthritis Market Juvenile Rheumatoid Arthritis Market Insights, Epidemiology, and Market Forecast-2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key juvenile rheumatoid arthritis companies including Novartis, AbbVie, Eli Lilly and Company, Sanofi, among others. Psoriatic Arthritis Pipeline Psoriatic Arthritis Pipeline Insight, 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key psoriatic arthritis companies, including Mylan, Celltrion, Pfizer, Amgen, among others. Psoriatic Arthritis Market Psoriatic Arthritis Market Insights, Epidemiology, and Market Forecast-2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key psoriatic arthritis companies including Mylan, Celltrion, Pfizer, Amgen, among others. 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