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Abstract Title: Sonic hedgehog in nasal mucus is a biomarker for smell loss in patients with hyposmia Background: Many chemical moieties have been identified in nasal and olfactory mucus related to cellular activity, cell signaling and olfaction. Sonic hedgehog (Shh) has been identified as a growth factor in taste buds but not in olfactory receptor tissues. We wished to determine if Shh were present in nasal mucus and, if present, does it relate to smell function and smell loss (hyposmia). Methods and findings: Shh was evaluated in nasal mucus in 14 normal volunteers and 44 patients with smell dysfunction of several etiologies. Nasal mucus was collected over a 1-4 day period in a 50 ml plastic container, transferred to a 12 ml plastic tube, centrifuged at 18,000 rpm for 45-55 minutes, the supernatant transferred to PCR tubes and frozen at 20°C until analyzed. All samples were analyzed by use of a sensitive spectrophotometric ELISA. Shh was found in nasal mucus in all normal subjects and in hyposmia patients. Levels in hyposmia patients of several etiologies were significantly lower than in normal. Levels decreased as subjects aged. Conclusions: This is the first systematic demonstration of Shh in nasal mucus in normal subjects and in hyposmia patients. Its presence is consistent with its role as a cell signaling moiety and growth or transcription factor related to olfactory receptor function. Its measurement in lower than normal concentrations in hyposmic patients may indicate that it can serve as a biomarker for smell loss in these patients. Its measurement can help to identify patients with hyposmic on an objective basis and help to define the biochemical parameters of their smell loss. Further studies can assist in determination of the specific role for this moiety in olfaction

Sonic Hedgehog in Nasal Mucus is a Biomarker for Smell Loss in Patients with Hyposmia