{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T16:01:41Z","timestamp":1763740901018,"version":"3.45.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The efficacy and safety of a novel cathepsin K inhibitor, VBX1000, were evaluated in client-owned dogs suffering from periodontal disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This open-label study recruited twenty dogs (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f20) with at least 3 teeth at stage 2 or 3 of periodontal disease. Dogs were orally treated once-a-day with VBX1000 (25\u202fmg\/kg or 50\u202fmg\/kg,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f10 per group) for 60\u202fdays, and then with 50\u202fmg\/kg once-a-day for an additional 30\u202fdays. The first objective was to assess evolution compared to pre-treatment of plasma carboxy-terminal telopeptide of collagen type 1 (CTX1) used as a marker of target engagement and bone resorption. In each evaluated tooth (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60; three teeth per dog), evolution counter to baseline of clinical attachment loss (CAL), periodontal probing depth (PPD), and bleeding on probing index (BPI) were evaluated The effects of cathepsin K inhibitor on alveolar bone defects were assessed with intraoral dental radiography (DR) performed at inclusion and at the end of the treatment period. A confirmatory analysis was performed in a subpopulation (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f10 dogs; 30 teeth) using the cone beam computed tomography scan (CBCT) imaging technique.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Throughout the treatment period, VBX1000 was well tolerated. At Day60, plasma CTX1 was significantly and similarly reduced compared with baseline (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05) in the two groups. At the end of the treatment period (at Day90) in the total population (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f20), plasma CTX1 was 0.10\u202f\u00b1\u202f0.04\u202fng\/mL relative to 0.26\u202f\u00b1\u202f0.20\u202fng\/mL at baseline (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). DR before and after treatment showed decreases in width (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60 teeth; three teeth\/dog;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001), depth (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05), and height of bone defects measured between the root and the maxillary bone. These effects on bone defects were confirmed in a subpopulation analyzed by CBCT. At the end of the treatment period, clinical attachment loss (CAL) was reduced relative to pretreatment: 2.87\u202f\u00b1\u202f1.73\u202fmm compared to 3.86\u202f\u00b1\u202f2.06\u202fmm (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001). Likewise, the periodontal probing depth (PPD) was reduced 2.71\u202f\u00b1\u202f1.03\u202fmm compared to 3.69\u202f\u00b1\u202f1.23\u202fmm (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings support the inhibition of cathepsin K by VBX1000 as a new therapeutic approach for mild-to-moderate periodontal disease in dogs. A randomized, double blinded placebo-controlled trial in dogs should confirm the potential of VBX1000 in this indication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2025.1656782","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T15:37:46Z","timestamp":1763739466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cathepsin K inhibition by VBX1000 alleviates canine periodontitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Jerzy","family":"Gawor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria 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