that topical compounds act on them directly to promote hair growth and antagonize androgen action. Large clinical studies showing effectiveness are absent. Topical treatment is also usually unavailable in North America. There is tentative evidence for cyproterone acetate in women. IGF-1 In December 2012, topical application of IGF-1 in a liposomal vehicle led to thicker and more rapid hair growth in transgenic mice with androgenic alopecia. The study did not show measurable systemic levels or hematopoietic side effects, suggesting potential for use in humans. Low energy radiofrequency irradiation induces IGF-1 in cultured human dermal papilla cells. Adenosine stimulates dermal papillae in vitro to induce IGF-1, along with fibroblast growth factors FGF7, FGF-2 and VEGF. β-catenin transcription increased, which promotes dermal papillae as well. Dietary isoflavones increase IGF production in scalp dermal papillae in transgenic mice. Topical capsaicin also stimulates IGF at hair follicles via release of vanilloid receptor-1, which in turn leads to more CGRP. Ascorbic acid has led to increased IGF expression in vitro. Stem cell therapy Although follicles were previously thought gone in areas of complete baldness, they are more likely dormant, as recent studies have shown the scalp contains the stem cells from which the follicles arose. Research on these follicular stem cells may lead to successes in treating baldness through hair multiplication (HM), also known as hair cloning. Per a May 2015 review, no successful strategy to generate human hair follicles, for hair regrowth, from adult stem cells has yet been reported. However, in April 2016, scientists from Japan published results of their work in which they created human skin from induced pluripotent stem cells; implanted into laboratory mice, the cells generated skin with hair and glands. Genetics From 2005 to 2007, Curis and Procter & Gamble collaborated on developing a topical hedgehog agonist for hair loss; the agent did not meet safety standards, and the program was terminated. In 2008, researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss. They found the gene P2RY5 causes a rare, inherited form of hair loss called hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth. Researchers found that disruption of the gene SOX21 in mice caused cyclical hair loss. Research has suggested SOX21 as a master regulator of hair shaft cuticle differentiation, with its disruption causing cyclical alopecia