Increasing Nasal Mucus Sonic Hedgehog (Shh) Improves Human Olfaction

Abstract

Sonic hedgehog (Shh) has been shown to act as a cell signaling and growth factor moiety in many tissues in humans and animals. Shh has not been associated with smell function. We therefore wondered if Shh played a role in human smell function and, if so, if it were present in nasal mucus. Thus, we measured Shh in nasal mucus in 14 normal subjects and in 44 patients with smell loss (hyposmia) of several etiologies by use of a sensitive spectrophotometric ELISA assay. Shh was found in nasal mucus in both normal subjects [7538±1105 pg/ml (M±SEM)] and in hyposmic patients (149±2 pg/ml) with levels in patients significantly lower than in normal subjects. These changes occurred in patients with losses of smell function related to post‐influenza‐like infection, allergic rhinitis and head injury. Treatment with oral theophylline 200‐800 mg daily for 2‐10 months significantly increased Shh levels in nasal mucus in hyposmic patients (49191±1710 pg/ml) and increased smell function significantly in over 60% of the patients. This is the first demonstration of Shh in nasal mucus. Its stimulation by theophylline resulted in improved smell function among hyposmic patients of multiple etiologies.