Nutraceutical Stimulation of Intrafollicular Autophagy as an Adjuvant Strategy in the Management of Alopecia Areata

Year: 
2019
PI Name: 
Ralf Paus, MD
Type:
Pilot & Feasibility Grant
Status: 
Active

Summary

This project will explore whether alopecia areata hair follicles display malfunctions in autophagy, which may make them more susceptible to immune-mediated hair follicle damage, and whether promoting hair follicle autophagy with nutraceuticals enhances human hair follicle growth and stress-resistance.

Abstract

Although novel treatments for alopecia areata (AA) such as JAK inhibitors can be efficacious, they are extremely expensive, may have long-term adverse effects, and don’t prevent AA relapse after therapy is discontinued. Therefore, new supportive AA therapies remain to be developed that also aid more permanent hair regrowth. Autophagy is a organelle and protein recycling process used by cells to facilitate growth and survival during stress. Recently, we have demonstrated that human scalp hair follicles (HFs) recruit autophagy to sustain their growth, while blocking HF autophagy inhibits human hair growth, Therefore, we propose to explore whether AA HFs display malfunctions in autophagy, which may make them more susceptible to immune-mediated HF damage, and whether promoting HF autophagy with nutraceuticals enhances human HF growth and stress-resistance. Specifically, we will investigate whether the expression of autophagy marker proteins and autophagolysosomes differ between healthy, non-lesional and lesional AA HFs. Next, we study whether interferon- the key cytokine in AA pathogenesis, modulates autophagy (i.e. LC3B and SQSTM1 expression and autophagolysosome generation) and whether inhibiting autophagy by LC3B gene-silencing prevents or promotes interferon-induced damage in organ-cultured human HFs. Finally, we will investigate whether enhancing autophagy by recognized enhancers of autophagic flux, i.e. the nutritional supplements caffeine and/or methylspermidine, makes cultured human HFs more resistant to interferon-induced HF damage and growth inhibition. These important pilot data will systematically introduce autophagy into translational AA research and is expected to identify a novel supportive therapeutic strategy in future AA management by nutraceuticals/cosmetics that targets autophagy.

Impact

If successful, this study may help inform new treatment strategies in alopecia areata through the use commercially available nutraceuticals that target autophagy.