Write in his international patent, L’Oréal said it has developed a method to in vitrothe prognosis and/or diagnosis of a “common alopecic condition of the scalp” by measuring the level of expression of very specific genes* involved in the intercellular junctions of the scalp and/or the hair follicle. He also described a in vitro method to assess the effectiveness of treating a common alopecic condition, including testing cosmetic treatments such as hair lotions, gels, shampoos and conditioners made using gene modulator and certain active compounds.
*Genes identified by L’Oréal: CDH1, ACTB, ACTBL2, TUBB, TUBB2A, GSN, MY03B, MY05B, MY06, DSG2, DSG3, DSG4, DSC2, GJB2, GJA1, GJB6, GJA3, TJP2, CLDN8, CLDN10, CLDN19, and possibly CTNNB1 and CTNND2
L’Oréal has indicated the prognosis, diagnosis and methods of treatment specifically related to common alopecia caused by disturbances of the hair cycle, as opposed to immune alopecia such as alopecia areata or localized baldness, universal alopecia areata and total alopecia areata. Evaluation and treatment could therefore be used for the likes of androgenetic alopecia, traction alopecia, hair loss in women, cicatricial alopecia, chemotherapy-induced alopecia or radiation therapy, telogen effluvium, stress-related alopecia, seasonal alopecia, age-related alopecia and micro-inflammatory alopecia.
Understanding Substantial Temporary or Permanent Hair Loss
“Natural hair loss can be estimated, on average, at a few hundred hairs per day for a normal physiological state”,the company wrote in its patent filing. “This process of constant physical renewal undergoes a natural evolution during aging: the hair becomes thinner and its cycles shorter. Various causes can, however, lead to significant hair loss, whether temporary or permanent,”L’Oréal wrote in its patent filing.
THE FOUR PHASES OF HAIR GROWTH AND RENEWAL
the anagen phaseor growth phase sees the hair follicle regrow hairs which will continue to grow until they are cut or reach the end of their lifespan. This is then followed by the catagen phase or transition phase where hair follicles shrink, hair separates from the bottom of the hair follicle and hair growth slows down. Next is the telegon phase or resting phase where hair growth ceases and hair loss begins at the end of this cycle. This is then followed by the neogen phaseor regeneration phase which loops back to the growth phase and sees the hair grow.
As L’Oréal explains: “The anagen phase, which is the active or growth phase during which the hair lengthens, lasts for several years. The very short catagen phase lasts a few weeks. The telogen phase or resting phase lasts for a few months. At the end of this rest period, the hair strands fall out and another cycle begins. The hair is thus in perpetual renewal and, of the approximately 150,000 strands of hair that make up a head of hair, approximately 10% are at rest and will be replaced in the months to come.
In common alopecia states, L’Oréal has stated that there are disturbances in the anagen or growth phase of the hair cycle, with a shortening of this phase; a gradual thinning of the hair strand; and a decrease in the amount of hair thereof. “A progressive miniaturization of the bulbs takes place, associated with an isolation of these bulbs by progressive thickening of the collagen matrix of the external conjunctiva sheath. Revascularization around the hair follicle is thus made more difficult cycle after cycle. The hair regresses and becomes miniaturized until it is no more than an unpigmented down, and this phenomenon leads to a progressive thinning of the hair.
Overall, this type of hair loss tends to affect very specific areas that typically differ between men and women, L’Oreal said, with hair loss in the temporal or frontal region in men and diffuse crown alopecia in women. In some cases, these men and women are genetically predisposed to hair loss, but in other cases, hair loss may be seasonal or accentuated by hormonal imbalance, physiological stress or malnutrition.
“In general, any factor that influences these processes, i.e., acceleration of cycle rate, progressive miniaturization of bulbs, progressive thickening of the perifollicular collagen matrix, thickening of the outer connective sheath, and decrease vascularization, will have an effect on the growth of hair follicles”, writes L’Oreal.
Identifying “new biomarkers” in male pattern hair loss
It was therefore important, according to the company, to find “new biological pathways” and “new biomarkers” to detect an alopecic state of the scalp, in particular before it is visible, in order to be able to reduce and/or slow down hair loss. Specifically, L’Oréal stated that there was a “significant need”for this in androgenetic alopecia – the loss of hair in both men and women which has occurred very characteristically in well-defined patterns. Targeting this common form of alopecia, especially in men, he said, was the goal of these inventions.
The beauty major said she discovered that the expression of specific genes identified, involved in the intercellular junctions of the cells of the scale and/or the hair follicle, such as keratinocytes and fibroblasts, was decreased in the area where the male or female -pattern hair loss was progressing. The measurement of the expression of these genes in these areas of the scalp has therefore made it possible to establish a prognosis and/or a diagnosis in a subject, he specifies.
The expression of these genes could then also be measured after a treatment intended either to induce and stimulate hair growth, or to slow down hair loss, to measure the effectiveness, obtained by the inclusion of modulators or active compounds in topical.
Proving the effectiveness of topical, oral and physical treatments against hair loss
These measurements, L’Oreal said, could be taken by taking a scalp biopsy or biopsy of one or more of the hair follicles and compared to control measurements to check “statistically significant” differences in gene expression. A treatment could be considered effective, the company said, if expression of a specific identified gene was increased after treatment, compared to before treatment and compared to a control level. Comparing more than one gene expression was preferable when testing a product’s effectiveness on androgenetic alopecia, he said.
“A treatment will be considered to have no effect if the expression levels of the chosen gene, before and after treatment, are substantially identical, or if the differences observed are not significant. writes L’Oreal.
Beyond topicals, these tests could also be used to measure the effectiveness of oral and physical treatments if needed, the company said. It was also possible to “evaluate the effectiveness of the combination of several treatments” – evaluating which combinations best restored gene expression levels of one or more of the identified genes, he said.
New treatments and combinations versus the effectiveness of existing products
L’Oreal said its inventions could be used to shape future innovations or qualify the effectiveness of existing products and treatments.
“In this way, combinations of treatments capable of being particularly effective, synergistic or complementary can also be considered”, It is said.
Source: WIPO International Patent No. WO/2022/003041
Filed: June 30, 2021. Posted: January 6, 2022.
Title: “Molecular signature of a common alopecic condition, associated with cell junctions”
Authors: L’Oréal – Y. Mahe, K. Bakkar and E. Bou Samra