Skin, with its densely packed layers of cells and lipids, keeps foreign substances from leaking in and water from leaking out. It's a reverse raincoat for our organs.
In ichthyosis and other skin diseases, this barrier breaks down, and problems arise. Unlike more commonly known skin diseases, in ichthyosis thick layers of scales can build up because the lipid-synthesis process in the skin goes awry. Besides causing discomfort and a scaly appearance, the condition can make the skin prone to secondary infections.
No effective treatments currently exist.
Using dogs that were born with one form of the disease, a new study uncovered its cellular and metabolic basis and used that information to create a compound to address the lipid deficits seen in the disease. Creating a lotion applied to the skin, they were able to reinstate the corneocyte lipid envelope (CLE) that is typically lacking in these patients.
A topical treatment is not a cure--toxic byproducts of fatty acid synthesis remained in the skin, but it's progress. The team began investigating the skin disorder in 2007 and discovered that puppies under had a mutation in the NIPAL4 gene, also called ichthyin. Later a human patient was found to have essentially same mutation in the NIPAL4 genes as the dogs. The mutation caused both humans and dogs to lack the NIPAL4 protein.
Studying the dogs with the mutation, in partnership with the company cyberDERM, the researchers found that the skin condition in the dogs mirrored that seen in human patients; their skin barrier was leaky so it lost water at higher rates than normal. The dogs also lacked the primary component of the CLE, a lipid called omega-hydroxy ceramide, and thus failed to form the lipid envelope that acts as the skin's water barrier.
Finally, the researchers discovered the presence of non-esterified free fatty acids, lipids that were being overproduced as the body's way of compensation for the defects in lipid production. Unfortunately, instead of acting to block water loss, these fatty acids "acted as a detergent in the cytoplasm of the cells, stripping even more water from the cells on the outer layer of skin.
The researchers worked with the Korean company Neopharm to produce a lipid-containing lotion aimed at restoring the CLE. While applying it to the skin didn't show great clinical improvements, examining a skin biopsy using high-powered microscopy revealed that it did reform the CLE. The researchers next goal will be to block the accumulation of fatty acids that contribute to the water loss and cell-membrane stripping.