Therapy for alopecia areata in mice using parathyroid hormone agonists and antagonists linked to a collagen-binding domain
The purpose of this study is to test the efficacy of parathyroid hormone-collagen binding domain (PTH-CBD), a compound that stimulates the hair cycle, in stimulating hair growth in the C3H/HeJ engrafted mouse model of alopecia areata.
In alopecia areata, the immune system damages the hair follicles, which causes hair loss and prevents the normal regrowth of hair after shedding. Parathyroid hormone not only regulates calcium and bone health, but also has effects on hair follicles, causing them to transition back into a growth phase. Parathyroid hormone has been shown to promote regrowth of hair after damage from chemotherapy, but because it is quickly absorbed into the blood, causing the blood calcium levels to rise which can cause kidney failure, it has been impractical to use as a treatment for hair loss. We have attached parathyroid hormone to a protein that is attracted to collagen in the skin. This new protein, called parathyroid hormone-collagen binding domain (PTH-CBD) is quickly absorbed into the skin collagen and continues to have effects more than a year after a single injected dose, with little or no effect on blood calcium levels. We tested PTH-CBD in mice which received chemotherapy, and found that hair loss can be prevented if the drug is given together with the chemotherapy, or treated if the drug is given after the chemotherapy. Given the way this new drug works, we think it is very likely that it can also be used to treat alopecia areata. In this proposal, we will perform the first round of testing, to see exactly what effects PTH-CBD has on hair growth in the C3H/HeJ mouse. We will test different doses of PTH-CBD to make sure we see the optimal response. We will also test another drug which blocks PTH effect. This drug has different effects on the hair cycle, and while it did not help chemotherapy-damaged hair regrow, it is possible it may prevent alopecia areata by providing protection from the immune system’s attack on the hair follicles. We will administer the drugs by injection just under the skin (subcutaneous injection), a manner which we know delivers them to the skin throughout the animal. Testing a drug which generates more hair follicles in a growth phase will allow us to learn more about how the damage progresses and how it is ultimately resolved. We expect that PTH-CBD will correct the defect by restoring the damaged follicles, promoting regrowth of hair and preventing additional hair loss in the future.
The final report shows PTH-CBD is a promising therapy for alopecia areata, particularly in conjunction with a mild immune suppressant, such as hydrocortisone cream.
- Katikaneni R, Gulati R, Suh D, Sakon J, Seymour A, Ponnapakkam T, Gensure R. Therapy for alopecia areata in mice using parathyroid hormone agonists and antagonists, linked to a collagen-binding domain. J Investig Dermatol Symp Proc. 2013 Dec;16(1):S61-2. doi: 10.1038/jidsymp.2013.25.
- Katikaneni R, Seymour AW, Gulati R, Ponnapakkam T, Gensure RC. Therapy for Alopecia Areata in Mice by Stimulating the Hair Cycle with Parathyroid Hormone Agonists Linked to a Collagen-Binding Domain. J Investig Dermatol Symp Proc. 2015 Nov;17(2):13-5. doi: 10.1038/jidsymp.2015.32.