Topical odorant application of the specific olfactory receptor OR2AT4 agonist, Sandalore^®, improves telogen effluvium-associated parameters

Background: Human hair follicles (HFs) express the olfactory receptor (OR)2AT4, which is selectively stimulated by the synthetic sandalwood-like odorant, Sandalore^®. In organ-cultured, human scalp HFs, Sandalore^® prolongs anagen and suppresses apoptosis by up-regulating intrafollicular IGF-1 mediated signaling. Aims: The objective of this study is to demonstrate whether effects of Sandalore^® observed ex vivo translate into a clinically relevant effect in patients with telogen effluvium. Patients/Methods: In a randomized, double-blinded, placebo-controlled, clinical trial, 60 female volunteers (18-65 years) affected by telogen effluvium received over a period of 24 weeks treatment with either 1% Sandalore^® solution (n = 30) or placebo (identically smelling, but non-OR2AT4 activating sandalwood oil n = 30). The study read-out parameters were the degree of hair shedding, hair volume, terminal/vellus hair ratio, anagen/catagen-telogen ratio, and patient self-assessment. Results: Sandalore^® 1% ameliorated clinical signs of telogen effluvium, namely it reduced hair shedding, and increased hair volume and the percentage of anagen HFs, the latter two parameters significantly more than placebo when changes were calculated to baseline. Sandalore^® also increased the ratio of terminal/vellus hairs at week 8. Most of the anti-hair shedding effects were seen after 8 weeks and maintained at week 24. Patient questionnaire showed that verum group patients were more satisfied than the placebo group in regard to the overall results. Conclusion: This clinical trial supports previous findings of anagen-prolonging effects of Sandalore^® ex vivo with similar results now reproduced in clinical practice. It also provides proof-of-principle that a topically applied cosmetic odorant acting through HF olfactory receptors can be a therapeutic alternative to treat hair loss disorders characterized by excessive hair shedding such as telogen effluvium.