{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:23:24Z","timestamp":1791591804850,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inhibition of Nod\u2010like receptor protein 3 (NLRP3) inflammasome within the central nervous system (CNS) is a promising therapeutic target for the treatment of Parkinson's disease (PD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This phase 1b open\u2010label study was conducted in elderly healthy volunteers (HV) and PD patients. The study was designed to assess safety and tolerability and to evaluate the central and systemic pharmacokinetic profile and anti\u2010inflammatory effects of a total daily dose of 300\u2009mg NT\u20100796 (oral 150\u2009mg suspension capsule formulation every 12\u2009h).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Four elderly HV and 10 subjects with PD received 150\u2009mg open\u2010label NT\u20100796 every 12\u2009h for either 7 or 28\u2009days, respectively. Blood and cerebrospinal fluid (CSF) were collected via serial sampling or lumbar punctures for pharmacokinetic and biomarker analyses. Standard safety parameters were monitored throughout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NT\u20100796 was safe and well tolerated with minimal adverse events. A reduced peak\u2010to\u2010trough ratio along with moderately higher exposure than the solution formulation (used in the first\u2010in\u2010human study) was observed, along with significant CSF exposure in elderly HV and subjects with PD. NT\u20100796 drove reductions in systemic inflammatory markers including high\u2010sensitivity C\u2010reactive protein, fibrinogen, interleukin (IL)\u20106, and IL\u201018. Furthermore, reductions in neuroinflammation, including IL\u20101\u03b2, were indicative of NT\u20100796's target engagement within the central nervous system (CNS) of subjects with PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CNS inhibition of NLRP3 with NT\u20100796 reduced neuroinflammation over a sustained 28\u2010day dosing period and demonstrates the potential for long\u2010term dosing of NT\u20100796 in future studies of patients with neurodegeneration. \u00a9 2025 NodThera Limited.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30307","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T12:00:57Z","timestamp":1755000057000},"page":"2199-2208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Anti\u2010Neuroinflammatory and Anti\u2010Inflammatory Effects of the\n                    <scp>NLRP3<\/scp>\n                    Inhibitor\n                    <scp>NT<\/scp>\n                    \u20100796 in Subjects with Parkinson's Disease"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9394-2353","authenticated-orcid":false,"given":"Nicholas","family":"Clarke","sequence":"first","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thornton","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Reader","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Lindsay","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Digby","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Mullen","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gorman","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Jacobson","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Langdon","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Johnstone","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Wheeler","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan P.","family":"Watt","sequence":"additional","affiliation":[{"name":"NodThera Ltd  Saffron Walden UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-223290"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182191"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23970"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112133"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.163359"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110358"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9988-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28015"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.10.062"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084148"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.11.010"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00476-2"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02371-0"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-023-01147-x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136722"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13576"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01398"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00109-6"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000512"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02830-w"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.123.002013"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2019.03.008"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000697"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.2742"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02122"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082481"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01092-6"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-94"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-9"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1213448"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.123.001941"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116455"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kew300"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75675-5"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.30307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T08:03:36Z","timestamp":1761465816000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.30307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/mds.30307"],"URL":"https:\/\/doi.org\/10.1002\/mds.30307","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"assertion":[{"value":"2025-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}