Initiation of Smell in Congenital Smell Loss

There are about 500,000 patients in the United States with congenital loss of smell, patients born without any sense of smell. The largest group of these patients have no gross brain abnormalities as determined by brain imaging, no anatomical abnormalities of the peripheral olfactory system as determined by nasal endoscopy, no other known congenital defects and no family history of smell loss. Congenital biochemical abnormalities of their olfactory system comprise several biochemical changes from normals: inhibition of secretion of nasal growth factors cAMP, cGMP and sonic hedgehog (Shh) which normally stimulate stem cells in the olfactory epithelium to initiate growth of olfactory receptors and activation of “death factors” TNFα and TRAIL which pathologically inhibit growth of olfactory receptors. We treated 19 of these patients, aged 6–61 years, with the phosphodiesterase inhibitor theophylline, 200–800mg daily for 2–36 months with smell function and nasal mucus growth and “death” factors measured at intervals of 2–10 months. Results indicated that smell function was initiated in 12 of these patients (63%) and quantified by both subjective return of smell function and by olfactometry. Significant increases in nasal mucus cAMP, cGMP and Shh and inhibition of nasal mucus TNFα and TRAIL occurred with theophylline treatment in these patients. Initiation of smell function occurred after theophylline treatment for 2–18 months and persisted as long as therapy was continued. This is the first report of initiation of smell function in patients with congenital smell loss. This initiation was associated with correction of congenital biochemical abnormalities in their nasal mucus growth and “death” factors. Support or Funding Information None