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Blocking FSH action prevents bone loss, fat gain, and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a K\n                    <jats:sub>D<\/jats:sub>\n                    of 7.52 nM. Using a Good Laboratory Practice (GLP)-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using\n                    <jats:sup>89<\/jats:sup>\n                    Zr-labeled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. The MS-Hu6 displayed a \u03b2 phase t\n                    <jats:sub>\u00bd<\/jats:sub>\n                    of 7.5 days (180 hr) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. The MS-Hu6 showed the same level of \u201chumanness\u201d as human IgG1 in silico and was non-immunogenic in ELISpot assays for IL-2 and IFN-\u03b3 in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing.\n                  <\/jats:p>","DOI":"10.7554\/elife.78022","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T08:00:58Z","timestamp":1663660858000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.78022","source":"Crossref","is-referenced-by-count":40,"title":["FSH-blocking therapeutic for osteoporosis"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-6259","authenticated-orcid":true,"given":"Sakshi","family":"Gera","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Translational Medicine and Pharmacology and The Mount Sinai Bone Program, Departments of Medicine and of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai","place":["New York, United 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