There may be hope for better treatment options of atopic dermatitis. 

A study conducted by L’Oréal Research & Innovation with the department of dermatology at the Hospital Saint-Louis in Paris may potentially improve the quality and efficacy of cosmetic products to treat the inflammatory skin disorder. 

Sonia Bouayadi PhD, Industrial Agreement for Training through Research at L’Oréal, presented the study at the International Federation of Societies of Cosmetic Chemists (IFSCC) Congress, which was held at the Palace of Festivals and Congresses of Cannes on Sept. 15-18.

“Our protocol is bold and stands out from existing literature,” she said. “We chose to look at the skin biome from a multi-scale perspective.”

She called atopic dermatitis or (AD) a “fascinating, complex disorder” that is a chronic inflammatory skin disorder with flare-ups and remissions of pruritic skin lesions. It’s also among the most common dry skin disorders that carries a profound effect on quality of life in the 10% of adults and 15%-20% of babies afflicted. In adults, major risk factors for the skin condition vary from climate to genes, diet and lifestyle choices, pollution and stress. 

While there’s no cure for AD, treatment for children has included bathing with a gentle cleanser, keeping the child’s fingernails short and moisturizing the skin. In adults, stress management and topical nonprescription creams containing 1% hydrocortisone have been proven to temporarily relieve the associated itch.

PLUMBING THE DEPTHS OF AD WITH RAMAN SPECTROSCOPY

Success in understanding the complexity of the skin disorder and targeting the skin microbiome is the key to unlocking an efficient cosmetic solution, Bouayadi said.

She said the scaly lesions associated with AD lead to a colonization of the skin by pathogens and bacteria and the disruption of function in the stratum corneum. The stratum corneum is the outermost layer of the epidermis and marks the final stage of keratinocyte maturation and development. Keratinocytes at the basal layer of the epidermis are proliferative, and as the cells mature up the epidermis, they slowly lose proliferative potential and undergo programmed destruction, per the National Institutes of Health. 

Bouayadi conducted an innovative study with Edouard Raynaud MD; Jocasta Avila PhD; Eric Arbey, Geraldine Rolland PharmD; Carine Baltenneck; Elodie Rieux; Barbara Lynch PhD Anne Saussine MD; Jean-David Bouaziz MD, PhD. The team used only non-invasive techniques with the goal to innovate and investigate the affected skin in 80 subjects compared with healthy subjects. Subjects were curated through the department of dermatology of Saint-Louis Hospital in Paris. Scientists measured the biological functions of healthy and AD skin. Biological functions refer to a series of individual processes accomplished by ordered assemblies of molecular functions, such as glycolysis or apoptosis, which are defined within the biological process ontology of the Gene Ontology initiative.

In the subjects with AD, the scientists found that the skin no longer plays its role of protecting the skin from external environment and retaining water from evaporation. To understand this process, they applied Raman spectroscopy. It is a developed analytical approach that can enable the noninvasive characterization of biological samples with a high degree of spatial resolution. In this process, an incident laser is used to excite samples, at which time Rayleigh (elastic) and Raman (inelastic) scattering can occur. The technique works by measuring the unique “chemical fingerprint” of a substance, which is based on the vibrational modes of its molecules. This fingerprint can be used to identify, characterize and quantify a wide variety of chemical components in both organic and inorganic materials.

The non-invasive technique provides “precious information” such as skin lipid content and lipid organization of the stratum corneum, Bouayadi said. 

“Thanks to this technique, we have demonstrated that the total lipid content was decreased not only in atopic lesions, but also in non-lesions compared to the control,” she said. 

Next, the team measured the lipid packing density; this was also decreased in atopic skin lesions and non-lesions. In the subjects with AD, it is less dense and less organized, Bouayadi noted. 

PROBING CERAMIDE’S ROLE

In the subjects with AD, the team found this lack of density could be among the fundamental causes of the loss of functionality of the skin barrier. To understand the attribution to the lack of density, the team found the answers in an analysis of ceramides. Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer.

After structural analysis, the team found an increased amount of short-carbon chain ceramides in atopic skin. The team surmised this shortage of ceramides could be linked to a loss of density of the lipid packaging they observed with the Raman spectroscopy.

From a structural point of view, the team evaluated the ratio of saturated over unsaturated protein-bound ceramides. The team found there was an increase of unsaturated ceramides. Saturation is responsible for membrane rigidity. The unsaturated ceramides present in atopic skin leads to a less rigid barrier, Bouayadi said.   

Taking it a step further, the team studied hydroxyl groups, and evaluated the evidence of three hydroxyl-free ceramides. Hydroxyl groups are a functional group found in sugars and alcohols. Bouayadi said they are decreased in atopic lesions. The team made the same observation in protein-bound ceramides. 

“This is important because hydroxyl groups can be responsible for membrane rigidity and functionality as they bind with high intensity to other molecules,” said Bouayadi. “In atopic skin, and especially in atopic lesions, a weakened skin barrier can’t be caused by a decreased amount in hydroxylated ceramides.”

With this information, the team sought to understand the cause of this ceramide composition and structural default. The team then delved into ceramide metabolism and a specific ratio of various free ceramide species. In examining the ceramides that are dehydroxylated, the team found that three hydroxylated ceramides are responsible for membrane rigidity and skin biome function. 

“There might be a direct link between the loss of functionality of skin barrier in 80 subjects linked directly to a metabolic defect,” said Bouayadi. “Our hyper thesis [found] there is a dysfunction in the activity for gene expression … that can lead to ceramide composition and a structural defect in 80 subjects.”

This approach led the team to identify two enzymic targets, which Bouayadi called a “real hope” for AD treatment in the near future.

She said the team plans to validate these enzymatic targets by testing the activity in vitro with AD reconstructive skin models, and identify new cosmetic molecules to modulate the enzymatic activity to repair the skin microbiome. 

This approach, she said, could be applied to other skin disorders like acne, opening the door to scientific discovery and cosmetic innovation.