THERAPY FOR CHEMOTHERAPY ALOPECIA WITH PTHRP ANALOGS

本研究的目的是开发一种新的方法来预防和治疗化疗引起的脱发。这是通过评估局部给予甲状旁腺激素相关肽（PTHrP）受体激动剂或拮抗剂的安全性和有效性，接受环磷酰胺的小鼠。结果表明，局部应用PTHrP拮抗剂环磷酰胺治疗前后显着减少环磷酰胺引起的毛囊营养不良的变化。在环磷酰胺治疗前后局部应用PTHrP受体激动剂增强环磷酰胺诱导脱发的作用。在环磷酰胺治疗之前和之后局部施用PTHrP受体拮抗剂或激动剂的长期效果的评价导致与接受环磷酰胺和每天局部施用安慰剂乳膏的小鼠组相比，接受环磷酰胺的小鼠的毛发更快速地再生长。拟定商业应用：本研究的结果为PTHrP受体拮抗剂的商业化提供了可能，该拮抗剂用于缓解接受化疗的患者的脱发。此外，局部PTHrP受体激动剂和拮抗剂可以在商业上开发，以加速接受化疗并具有显著脱发的患者的毛发再生。

The goal of this research program is to develop a new approach for preventing and treating chemotherapy induced alopecia. This is being accomplished by evaluating the safety and efficacy of topically administering a parathyroid hormone related peptide (PTHrP) receptor agonist or antagonist to mice that received cyclophosphamide. Results suggest that the topical application of a PTHrP antagonist before and after cyclophosphamide treatment markedly reduce the dystrophic changes induced by cyclophosphamide on the hair follicle. The topical application of a PTHrP receptor agonist before and after cyclophosphamide therapy enhanced cyclophosphamide effect on inducing alopecia. An evaluation of the long term effect of topically applying a PTHrP receptor antagonist or agonist before and after cyclophosphamide therapy resulted in a more rapid regrowth of the hair on mice that received cyclophosphamide compared to the group of mice that received cyclophosphamide and the daily topical application of a placebo cream. PROPOSED COMMERCIAL APPLICATION: The results from this study offer the potential for the commercialization of a PTHrP receptor antagonist for the mitigation of hair loss in patients who are treated with chemotherapy. In addition, topical PTHrP receptor agonist and antagonist can be commercially developed to accelerate hair regrowth in patients who receive chemotherapy and have significant hair loss.