The hair follicle as a target for gene therapy

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Ann Dermatol Venereol 2002 May;129(5 Pt 2):841-4

The hair follicle as a target for gene therapy

The hair follicle possesses progenitor cells required for continuous hair follicle cycling and for epidermal keratinocytes, melanocytes and Langerhans cells. These different cell types can be the target of topical gene delivery in the skin of the mouse. Using a combination of liposomes and DNA, we demonstrate the feasibility of targeting hair follicle cells in human scalp xenografts. We consider liposome composition and stage of the hair cycle as important parameters influencing transfection of human hair follicles. Transfection is possible only during the early anagen phase. Factors and obstacles for the use of gene therapy in treating alopecia and skin diseases are discussed. A theoretical framework for future treatment of cutaneous and systemic disorders using gene therapy is presented.

Dermatology 2002;205(2):108-10

Kenogen. A new phase of the hair cycle?

BACKGROUND: A novel phenomenon has been described by the phototrichogram: the emptiness of the follicle after teloptosis. We called this phenomenon kenogen, from the Greek kappaepsilonnuovarsigma, 'empty'. OBJECTIVE: To describe the kenogen phase in its details. METHODS: Analysis of the existing literature. RESULTS: The original observation in 2 women was confirmed in 10 balding and non-balding males studied for 14 years in whom kenogen lasted about 4 months increasing up to about 7 months and affecting 80% of all hair cycles. In 2 women with progressing androgenetic alopecia studied for 2 years, kenogen involved 22% of the hair follicles, lasting from 3 months to 1 year. In a prepubertal boy studied for 1 year, it involved 8% of hairs and lasted about 2 months. CONCLUSION: During kenogen, the hair follicle rests physiologically, but duration and frequency are greater in androgenetic alopecia, possibly accounting for baldness. In addition to the classical cycle, the hair follicle may follow an alternative route during which the telogen phase, not accompanied by a coincident new early anagen, ends with teloptosis leaving the follicle empty.

Ther Umsch 2002 May;59(5):238-42

Hair loss in internal medical illnesses

Hair loss related to internal diseases is generally temporary and often fully reversible. An iron- or protein-deficiency induced hair loss may be cured by simple substitution. In acute internal diseases, fever and after operations the patient may expect complete recovery of the hair loss without therapy. Symptomatic alopecia due to chronic diseases has a different prognosis and is dependent on the severity and character of the underlaying disease. If the systemic disease can be cured the hair loss may be decreased. Treatment and diagnosis of the systemic disease is recommended to be performed in cooperation with experts of internal medicine, oncologists and specialists of endocrinology.

J Clin Endocrinol Metab 2001 Dec;86(12):5762-4

Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/dilution and mass spectrometry.

Production rates of dihydrotestosterone (DHT) were determined in healthy men (n = 8), in healthy women during the follicular phase of their menstrual cycle (n = 7), and in young men with male pattern baldness (n = 8) using the stable isotope dilution technique and mass spectrometry. [2,3,4-(13)C]DHT was infused for 10 h at doses of 15 microg/h (men) and 2 microg/h (women), and blood samples were obtained at 20-min intervals during the last 4 h of the observation period. Production rates estimated between April and June were 2.9 +/- 1.1 microg/h (women) and 17.8 +/- 6.2 microg/h (men). In men production rates of DHT were similar (16.2 +/- 7.7 microg/h) when the investigation was repeated between October and December. Mean production rates of DHT in young men with male pattern baldness (60 +/- 50 microg/h) were higher than those in healthy men (P < 0.005). Although this group included two individuals with normal production rates of DHT, the production rate of DHT was markedly elevated (range, 32.0-161.0 microg/h) in the remaining patients. Stable isotope-labeled infusions of DHT are suitable for clinical use in a routine setting to obtain analytically correct estimates of DHT production in vivo. In the majority of men with male pattern baldness endogenous production of DHT is markedly increased, providing a rationale for therapeutic 5 alpha-reductase inhibition in this disorder.

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