{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:37:07Z","timestamp":1792265827604,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Essential tremor is the most common movement disorder with clear unmet need. Mounting evidence indicates tremor is caused by increased neuronal burst firing and oscillations in cerebello\u2010thalamo\u2010cortical circuitry and may be dependent on T\u2010type calcium channel activity. T\u2010type calcium channels regulate sigma band electroencephalogram (EEG) power during non\u2010rapid eye movement sleep, representing a potential biomarker of channel activity. PRAX\u2010944 is a novel T\u2010type calcium channel blocker in development for essential tremor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Using a rat tremor model and sigma\u2010band EEG power, we assessed pharmacodynamically\u2010active doses of PRAX\u2010944 and their translation into clinically tolerated doses in healthy participants, informing dose selection for future efficacy trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Harmaline\u2010induced tremor and spontaneous locomotor activity were used to assess PRAX\u2010944 efficacy and tolerability, respectively, in rats. Sigma\u2010power was used as a translational biomarker of T\u2010type calcium channel blockade in rats and, subsequently, in a phase 1 trial assessing pharmacologic activity and tolerability in healthy participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In rats, PRAX\u2010944 dose\u2010dependently reduced tremor by 50% and 72% at 1 and 3\u00a0mg\/kg doses, respectively, without locomotor side effects. These doses also reduced sigma\u2010power by ~30% to 50% in rats. In healthy participants, sigma\u2010power was similarly reduced by 34% to 50% at 10 to 100\u2009mg, with no further reduction at 120\u2009mg. All doses were well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In rats, PRAX\u2010944 reduced sigma\u2010power at concentrations that reduced tremor without locomotor side effects. In healthy participants, comparable reductions in sigma\u2010power indicate that robust T\u2010type calcium channel blockade was achieved at well\u2010tolerated doses that may hold promise for reducing tremor in patients with essential tremor. \u00a9 2022 The Authors.\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.28969","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T02:58:31Z","timestamp":1646708311000},"page":"1193-1201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Translational Pharmacology of\n                    <scp>PRAX<\/scp>\n                    \u2010944, a Novel T\u2010Type Calcium Channel Blocker in Development for the Treatment of Essential Tremor"],"prefix":"10.1002","volume":"37","author":[{"given":"Liam","family":"Scott","sequence":"first","affiliation":[{"name":"Praxis Precision Medicines  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey B.","family":"Puryear","sequence":"additional","affiliation":[{"name":"Praxis Precision Medicines  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel M.","family":"Belfort","sequence":"additional","affiliation":[{"name":"Praxis Precision Medicines  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Raines","sequence":"additional","affiliation":[{"name":"Praxis Precision Medicines  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb A.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Praxis Precision Medicines  Boston Massachusetts 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