{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:29Z","timestamp":1792790369505,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Neurology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NINDS","award":["U01NS055903-13"],"award-info":[{"award-number":["U01NS055903-13"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Child Health and Human Development","award":["P50HD103556-04"],"award-info":[{"award-number":["P50HD103556-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Huntington\u2019s disease (HD) is an inherited neurodegenerative disorder primarily associated with motor and psychiatric manifestations. No disease-modifying treatment currently exists, with vesicular monoamine transporter type-2 inhibitors (VMAT2i\u2019s) being the only FDA-approved therapy for motor features in HD. Previous studies evaluated the antichorea effects of VMAT2i\u2019s but did not address its effects on non-choreiform features.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>\n                    This study aimed to characterize the effect of VMAT2i\u2019s on hyperkinetic, hypokinetic and total hypokinetic subscores of the UHDRS motor assessment in patients with motor-manifest HD from the\n                    <jats:italic>Enroll-HD<\/jats:italic>\n                    research platform.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data from 622 participants were analyzed. Linear mixed effects models were constructed to compare the rates of change of choreiform and non-choreiform motor scores before and after the initiation of a VMAT2i. We calculated and plotted the direction, magnitude and significance of VMAT2i administration on the rates of change of motor subscores. A similar analysis was performed investigating the effect of antipsychotic medications on motor subscales in HD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>VMAT2i\u2019s reversed progression of hyperkinesis but significantly increased the rates of change in the hypokinetic and total hypokinetic subscores. Antipsychotics also displayed efficacy in reversing progression of chorea but did not significantly influence progression of hypokinesis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The initiation of VMAT2i\u2019s was associated with an improvement in hyperkinesis but was associated with worsening of other motor features of HD. Hypokinesis increases progressively in HD and is correlated with functional impairment and global decline. Therefore, the use of VMAT2i\u2019s to treat motor features in HD should be a nuanced decision, considering its multipronged impact.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.26.26364085","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:30:22Z","timestamp":1790627422000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of Vesicular Monoamine Transporter Type-2 Inhibitors on Motor Features in HD"],"prefix":"10.64898","author":[{"given":"Nabil","family":"Halabi","sequence":"first","affiliation":[{"name":"Carver College of Medicine at the University of Iowa, Department of Psychiatry, 200 Hawkins Drive, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Killoran","sequence":"additional","affiliation":[{"name":"Carver College of Medicine at the University of Iowa, Department of Neurology, 200 Hawkins Drive, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peg C.","family":"Nopoulos","sequence":"additional","affiliation":[{"name":"Carver College of Medicine at the University of Iowa, Department of Psychiatry, 200 Hawkins Drive, Iowa City, IA 52242"},{"name":"Carver College of Medicine at the University of Iowa, Department of Neurology, 200 Hawkins Drive, Iowa City, IA 52242"},{"name":"Stead Family Department of Pediatrics at the University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100104100785000_2026.09.26.26364085v1.1","doi-asserted-by":"publisher","DOI":"10.1177\/0891988710383573"},{"key":"2026100104100785000_2026.09.26.26364085v1.2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.71476"},{"key":"2026100104100785000_2026.09.26.26364085v1.3","unstructured":"Suchowersky O. 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