STRC Research

STRC Rescue Threshold

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STRC rescue threshold

SUPERSEDED IN PART — dB/audiological outcomes QUARANTINED 2026-08-20. NOT-MODELABLE: Rescue threshold hearing outcome (20-30 dB ABR improvement) is withdrawn; outcome chain ungrounded. OHC recovery metrics at the protein level remain valid as open questions.

Any patient- or route-level hearing outcome stated below (dB thresholds, ABR values, MILD/MODERATE/NORMAL categories, “rescue to X dB”) is withdrawn as a stated result pending the provenance-and-runtime audit named in STRC Cure-Route Audit 2026-08-20. Reasons: the ABR transfer function’s calibration papers are absent from sources/lit/; models/mrna_lnp_audiogram_rescue.py and models/strategy_b_audiogram_rescue.py currently fail to execute (BROKEN 2026-08-20); and a scalar functional-OHC fraction cannot yield a frequency-resolved audiogram in any case. Not affected: primary-paper observations, prospective wet-lab success criteria, and protein-level/coverage arithmetic. Original text retained below as historical record.

Definition. Minimum fraction of OHCs that must express functional stereocilin (or receive protein) to produce clinically meaningful ABR improvement.

Working estimate (from 2021 Holt + 2026 Iranfar):

  • 30-50% OHC transduction → 20-30 dB ABR shift in mouse
  • 50-70% → approaching WT ABR threshold
  • <20% → undetectable effect

Translation to human.

  • Conservative target: 40% OHC rescue over apical-to-mid turns = expected 20 dB PTA improvement
  • Stretch: 60% rescue = 30+ dB improvement, approaching normal-range hearing

Used as gate in:

  • h04 mRNA-LNP PKPD (OHC tropism modeling)
  • h09 hydrogel (HTC restoration coverage)
  • All delivery-phase audits

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