The plot thickens (as the skin gets thinner)

A paper published online today in the Journal of Allergy and Clinical Immunology changes our picture of skin barrier defects in eczema. A large research group (from eight institutions, including six in the U.S. and two in Germany) has shown that there is another upper skin layer protein besides filaggrin that, when mutated, is a likely cause of eczema.

The newly fingered culprit, claudin-1, is a component of "tight junctions," which bind neighboring cells together and form a seal against permeating allergens and pathogens. Tight junctions occur in the layers of the skin BELOW the stratum corneum. It is in the stratum corneum that filaggrin performs its job of flattening skin cells and getting digested into "natural moisturizing factor."

The paper is pretty comprehensive. The scientists found that

• the skin of patients with eczema contains much less claudin-1 than skin from "normal" people 
• afflicted skin is much more porous to ions than normal skin
• knocking out claudin-1 from skin cells increases the permeability of a layer of these cells
• in patient samples, the less claudin-1 that is present, the higher the levels of IgE antibodies
• and, in a population study, there are several point mutations of the claudin-1 gene that are statistically associated with eczema.

There are also several aspects of the research that are important to patients with eczema:

I saw in the funding acknowledgements that the lead author, Anna De Benedetto, and the senior author, Lisa Beck, both from the University of Rochester (NY), were funded to some extent by the National Eczema Association. Go NEA!

In the research, the authors made extensive use of samples from the Atopic Dermatitis Research Network, which is the precursor of the Atopic Dermatitis Vaccinia Network (a $32 million behemoth of a project that is 100x larger than the average NIH-funded eczema grant).

And I note that the University of Rochester has applied for a patent for the concept of using drugs to stimulate claudin-1 expression in the skin as a method for eczema treatment. It's funny; I've spent time as an engineer in industry and I work all the time with technology transfer and startup companies, but I was raised in a family with decided socialist tendencies, one of these being a knee-jerk anti-industry outlook. Or maybe that's just me. While I've learned to see that not all capitalism is evil--for instance, what would I do without Aveeno, or the companies that manufacture my steroid ointment? And don't I like my iPhone and the MacBook I'm typing this on?--my immediate reaction upon learning that a university has taken out a patent is to think "The greedy so-and-sos."

But that is misguided. And I quickly readjust; a patent is absolutely necessary to protect the intellectual property in a case like this. In the end, if a claudin-1 stimulant is an effective treatment for eczema, it will be a company that has to develop it and take it through clinical trials, which are horrendously expensive. (The rule of thumb is that it costs $1 billion to get a new drug approved by the FDA.) No pharmaceutical company or venture capitalist will invest in a drug lead for which the intellectual property isn't secure. It is good for you and me that the University of Rochester has immediately begun the patent process.