The Biology of Hair and Hair Loss

RT1640 was created specifically to treat androgenic alopecia.  The science underlying the hair-regenerative activity of RT1640 is based on our understanding of the molecular and cellular biology of the hair follicle, hair growth and the stem cells of skin. The stem cells of the skin live in a structure that is part of the hair follicle, termed the “bulge”. During normal hair growth and development these stem cells migrate down along the inner aspect of the hair follicle toward another structure at the base of the follicle called the dermal papilla.  Signals from the papilla attract the migrating stem cells, and once nearby, the papilla provide additional signals instructing the stem cells to differentiate into hair, which then incorporate into the growing hair shaft.  The dermal papilla also make factors that support the health and survival of the hair. 


Hair Lifecycle

As depicted below, hair has 3 distinct phases in its normal lifecycle.  Anagen is the growth phase, which can last up to 6 years for any given strand of hair.  Stem cells in the dermal bulge remain undifferentiated.  This undifferentiated phenotype is maintained by the repression of the activity of the protein CDK4 by another protein, NFAT-c1.  During normal hair growth, the stem cells from the dermal bulge chemotact (are drawn) toward the dermal papilla by expression of a number of dermal papilla-expressed cytokines, including keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-2 (IGF-2) (Danilenko et al., 1995; Lin et al., 2015; Lindner et al., 2000; Rudman et al., 1997).  As the stem cells migrate toward the dermal papilla, NFAT-c1 expression is lost, leading to the de-repression of CDK4, and subsequent stem cell proliferation and differentiation into growing hair.  Certain drugs, including cyclosporine A inhibit NFAT-c1 activity, leading to precocious anagen and exuberant hair growth.

At any one point, about 1% of the hair follicles are in catagen, a transitional short-lived phase in the hair life cycle.  During catagen, the dermal papilla moves upward into the upper portion of the follicle, effectively shrinking the follicle, but pushing it upward, causing a lengthening of the external portion of the hair shaft.  It is notable that during catagen, the melanocytic progenitor cells die, leading to gray hair.  Soon thereafter the follicle enters telogen, when the dermal papilla separates from the follicle, essentially cutting off the supply of both growth factors and blood.  This leads to the loss of the hair shaft, and the follicle enters a dormant phase lasting 2-4 months. After a resting period anagen restarts unless a pathology is present, such as androgenic alopecia.


Androgenic alopecia (AGA)

Both men and women make the sex hormone testosterone.  Testosterone is metabolized to many active forms, one of which is dihydrotestosterone, or DHT.  While DHT is a potent activator of many androgenic pathways, it is also toxic to the dermal papilla. DHT-mediated loss of the dermal papilla has profound negative effects on both the survival of existing hair as growth factor (nutrient) support is lost., In the absence of the dermal papilla the follicle is unable to make the transition from catagen to anagen.   Compounds, such as Minoxidil protect the dermal papilla while the follicle is in anagen, but they are not sufficient to drive the follicle from catagen to anagen in the setting of AGA. Once the hair is lost owing to the effects of DHT, the follicles atrophy, and they remain as shrunken structures within the scalp for decades.  As we show below, these can be reanimated and induced to grow new hair by treatment with RT1640.