Topical Thyroid Hormones for Hair Regrowth
The study tests whether FDA-approved, topically-applied T3 and T4 promote the production of key growth factors, metabolism, and stem cell activities on human scalp skin to treat androgenic alopecia.
Project Team
Institutions
Project Status
Funding Opportunity
Background
Past research on two drugs of interest in the thyroid hormone family, triiodothyronine (T3) and thyroxine (T4), has shown that both can prolong the anagen phase of the hair follicle cycle or mitigate hair stem cell apoptosis (desirable traits of hair loss treatments). The synthetic versions of T3 and T4, l-triiodothyronine and l-thyroxine, have well-documented pharmacokinetics, as they are both frequently prescribed orally today for hypothyroidism. While T4 is converted intracutaneously into T3 by the deiodinase enzyme, T4’s additional downstream pathways may also play a role in its hair growth effects. The proposed project would be conducted on human scalp skin in a 3-D organ culture, building off Paus et. al’s 2008 study on human hair follicles in organ culture. The primary differences between the previous ‘08 and the current study are the organ tested and the application method: the ‘08 study was tested on hair follicles extracted from the scalp through a solution infused into the culture itself, whereas our study would be tested on scalp skin through a topical solution resembling already a potentially practicable application method. In the ‘08 study, T4 increased hair matrix keratinocyte proliferation and prolonged the anagen phase of the hair follicle cycle, while T3 mitigated hair matrix keratinocyte apoptosis.
Project Details
In order to decrease the risk of side effects, both T3 and T4 would be administered in pulse therapy, applied for several consecutive days followed by a prolonged period without administration. The total cost of the study would be $125 thousand dollars, dependent on additional readings obtained. The study would be conducted over 12 months, tested on scalp skin samples from three separate human donors. Our two primary testing doses are 100 pM of T3 (77.69 mcg) and 100 nM of T4 (0.065 mcg), the two most effective doses elucidated in the ‘08 study. Additionally (4-6 months later), we will test other dose regimens for each thyroid hormone, with the range determined by the initial toxicology metrics exhibited by each hormone’s primary doses. Finally (after an additional 2-4 months), we would test a combination therapy of T3 and T4, determined by the data generated from monotherapy. Each dose would be administered over a varied number of consecutive days. The efficacy and toxicology of all tests, conducted on human scalp skin in organ culture, will be measured by: Ki-67/caspase 3 (proliferation/apoptosis) keratin 15, keratin 15/Ki-67, Keratin 15/caspase 3 (epithelial HF stem cells) Warthin-Starry histochemistry (melanin production, also used for hair cycle staging & HF toxicity assessment) H&E histochemistry (hair cycle staging, HF morphology, HF toxicity) IGF-1, TGFß2, FGF7/KGF (key growth factors) K85 (key hair shaft keratin) CD31, VEGF-A (angiogenesis if stimulated–this will keep HFs longer in anagen and may promote vellus-to-terminal HF reconversion after long-term application in vivo). p-S6 expression (mTorC1 activity) MTCO1 expression (mitochondrial activity). Standardized photography (to assess hair shaft production after 6 days topical T3 and T4 application).
Project Timeline
Primary Dose Data Collection
Required Funding$75,000
Statusongoing
Duration6 MonthsThe first 4-6 months of our projected year-long study will generate our dataset for two topical separate solutions containing our two primary testing doses, 100 pM of T3 (77.69 mcg) and 100 nM of T4 (0.065 mcg). This step requires an additional $25,000 at completion, after which we would test two additional doses and a combination dose, if desired (for an additional $18,750).