{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:43:58Z","timestamp":1780595038507,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT\u2010020, a novel compound to improve mitochondrial function, in a 2\u2010part study in early stage HD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Part 1 consisted of 7\u2010day multiple ascending dose study to select the highest tolerable dose for Part 2, a 28\u2010day multiple dose study. Mitochondrial function was measured in the visual cortex and calf muscle, using phosphorous magnetic resonance spectroscopy, and in circulating peripheral blood mononuclear cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment\u2010emergent adverse events were mild and more present in the SBT\u2010020 group. Injection site reactions occurred in 91% in Part 1 and 97% in Part 2. Mitochondrial function in calf muscle, peripheral blood mononuclear cells or visual cortex was not changed overall due to treatment with SBT\u2010020. In a <jats:italic>posthoc<\/jats:italic> analysis, patients with a higher degree of mitochondrial dysfunction (below the median [\u2206\u03a8<jats:sub>m<\/jats:sub> &lt; 3412 and \u03c4PCr &gt; 42.5 s]) showed more improvement than patients with a relatively lower level of mitochondrial dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SBT\u2010020 was safe at all doses, but no significant differences in any of the pharmacodynamic measurements between the treatment groups and placebo group could be demonstrated. The data suggest that the better than expected mitochondrial function in our patient population at baseline might explain the lack of effect of SBT\u2010020.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14656","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T17:16:51Z","timestamp":1605547011000},"page":"2290-2302","source":"Crossref","is-referenced-by-count":8,"title":["Safety, pharmacokinetics and pharmacodynamics of SBT\u2010020 in patients with early stage Huntington's disease, a 2\u2010part study"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6708-1082","authenticated-orcid":false,"given":"Marcus P.J.","family":"van Diemen","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen P.","family":"Hart","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The 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