Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving oxidoreductase
Patent
1993-10-19
1995-08-22
Wityshyn, Michael G.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving oxidoreductase
435 25, 435 28, 436 63, 436 86, 436904, 514880, C12Q 130, C12Q 126, C12Q 128, G01N 3348
Patent
active
054439612
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns a procedure for diagnosis of an inflammatory or cell-aging state in keratinocytes, or of the efficacy of a treatment designed to combat said cell aging or inflammation.
It is known that the epidermis is composed of cells called keratinocytes, which are continuously regenerated by division at the basal cell level and which become gradually differentiated and undergo modification so as to form a layer of keratinized cells, ultimately producing the stratum corneum, which consists of dead cells making up the outermost layer of the epidermis.
It is also known that hairs are produced in hair follicles formed from epithelial sheaths of epidermal origin and from a bulb (matrix) containing bulbar keratinocytes in a state of continuous division during the growth phases of the hair (anagenetic phase), these growth phases alternating with the resting phases, during which the hair ceases to grow and then "falls out" naturally. Following the natural loss of this hair, the underlying papilla forms a new hair follicle, and the cycle is repeated.
It has been observed, mainly in men, that in the zone forming the top of the skull (vertex), the hair-production cycles sometimes stop prematurely. This phenomenon is termed alopecia, which is not found in the peripheral areas of the skull, and, in particular, the back of the neck.
It is known that these alopecia phenomena are accompanied by various modifications of the keratinocytes of the hair follicle, in particular of the proportions of glutathione or glutathione peroxidase, which diminish in subjects in which the alopecia is well established (see, in particular, M. Kermici et al., IFSCC Congress, New York, October 1990).
It has now been discovered that these changes, which signify a state of cell aging, are already present in subjects not yet suffering from alopecia or who suffer from mild alopecia. The same is true for catalase activity (catalase being present in the keratinocytes of the hair follicles), which is increased in hair follicles located in the "alopecia zone" of subjects having alopecia or of those in whom is it latent.
By measuring the activity of these various markers of cell aging and by comparison with the proportion of these markers in hair follicle keratinocytes in zones not afflicted with alopecia (back of the neck), it is possible to detect pre-alopecia states making it possible to predict whether a given individual is liable to "lose his hair" prematurely.
It is known, moreover, that alopecia can be combatted, in particular by using minoxidil. However, treatment with minoxidil is not effective in some non-responding persons (about 40% of the cases treated).
Minoxidil causes, in particular, restoration of the equilibrium of the enzymatic activities between the hair follicles in the vertex and in the back of the neck. However, this restoration of balance is not observed in some subjects (responding subjects), while, in others (non-responding subjects), a restoration of this kind is not found.
These changes in enzymatic activity, especially in subjects predisposed to alopecia, can be reversed by treating with minoxidil, generally after approximately three to six months of activity.
However, it has been discovered that this desirable effect, i.e., the restoration, using minoxidil, of the balanced activity of glutathione peroxidase or of the concentration of glutathione in the hair follicles in the vertex area is possible only if this activity or concentration has not already been excessively disrupted prior to treatment, since, at that point, restoration of equilibrium using minoxidil can no longer be obtained. According, when the ratio of the concentrations or activities of these markers of aging in the zone tested and in the non-pathological control zone is greater or, depending on the case, lesser, than a certain threshold (which may be established by routine experiments), it then becomes possible using the invention procedure to determine whether treatment using minoxidil will be effective in a given individual.
With respec
REFERENCES:
patent: 4898813 (1990-02-01), Albarella et al.
Aldrige "Hair Loss" Brit. Med. J. 289: 985-989 1984.
Yohn et al. "Disparate Antioxidant Enzyme Activities in Cultured Human Cutaneous Fibroblasts, Keratinocytes & Melanocytes" J. Invest Dermatol 97(3)405-409 Mar. 1991.
M. Kermici et al, "Evidence for an age-correlated change in glutathione metabolism enzyme activities in himan hair follicle", Mechanisms of Ageing and Development, vol. 53, No. 1, Mar. 1990, pp. 73-84.
Kermici Michel
Pruche Francis
Prunieras Michel
"L'Oreal"
Degen Nancy J.
Wityshyn Michael G.
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