{
  "id": 8169763,
  "title": "Comprehensive preclinical reevaluation of PaBQU and DBQU regimens identifies lesional liability in hard-to-treat forms of tuberculosis",
  "url": "https://urgent.news/2026/09/17/comprehensive-preclinical-reevaluation-of-pabqu-and-dbqu-regimens",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-17T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751879v1?rss=1"
  },
  "original_language": "en",
  "account": "A recent report has identified a potential obstacle in the development of preclinical tuberculosis treatment regimens, specifically those containing PaBQU and DBQU. These regimens, which were part of a human Phase 2 trial, failed to meet the treatment shortening criteria within the Target Regimen Profile (less than 3 months). Researchers hypothesized that the slow or diminished onset of effect in complex lung lesions may have been the cause of this early termination. To investigate this theory, they conducted a translational study, comparing the easy-to-treat BALB/c mouse, with less complex lesions, to the hard-to-treat C3HeB/FeJ mouse, which develops more human-like lesions. The study evaluated traditional and novel pharmacodynamic markers, relapse outcomes, and ex vivo caseum pharmacokinetics. The results showed that PaBQU and DBQU were slower to elicit bactericidal activity, RS ratio activity, and prevent relapse in the C3HeB/FeJ mouse compared to the BALB/c mouse. A reference regimen, BPaMZ, exhibited less lesional liability than PaBQU and DBQU. The study suggests that the slower accumulation of bedaquiline in caseum, a key component of PaBQU and DBQU, may contribute to their reduced efficacy in hard-to-treat forms of tuberculosis. The researchers recommend a systematic examination of additional diverse regimens to determine the potential of preclinical lesional liability as a predictor of clinical treatment shortening activity.",
  "summary": "Murine efficacy models inform advancement of preclinical tuberculosis treatment regimens to human clinical testing. A recent human Phase 2 trial was terminated early because investigational regimens (4-months of PaBQU or DBQU) did not meet the treatment shortening criteria outlined in the Target Regimen Profile ([≤] 3 months). We queried whether a factor leading to this early termination may…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}