Lately I’ve been thinking a lot about skin. I have two teenage daughters learning about makeup and an 11-year-old son with whom I’ve had several recent conversations about the importance of regular face washing. I guess my talks worked, since they’re now all regularly stealing my packages of facial wipes and hiding them from one another!
Our family has pretty good skin in general, and we’re lucky that all we have to deal with is an occasional acne flare-up. But I remember other relatives who’ve struggled with psoriasis: itchy, scaly patches of skin that just won’t go away. In severe cases the symptoms, which are caused by chronic inflammation, can cover large areas of skin and are accompanied by arthritis in nearby joints and an increase risk of stroke or heart attack.
Psoriasis has a genetic component but is triggered by environmental conditions such as wounding or by the bacteria that causes strep throat. Unfortunately there are few effective treatment options for it, though some patients resort to long-term immunosuppression to manage their symptoms. Now, though, dermatologist Peter Marinkovich, MD, who directs Stanford’s Blistering Disease Clinic, and postdoctoral scholar Marten Winge, MD, PhD, have identified a small molecule in the skin that could be an effective target for new therapies. They published their research today in the Journal of Clinical Investigation.
As Marinkovich explained in our release:
Normally there’s a quiet, ongoing conversation between the epidermis and our immune system as they work together to fight disease such as infections. In psoriasis, this has escalated into an uncontrollable shouting match that results in abnormal cellular proliferation, scaling and inflammation with no real effective therapies other than long-term immunosuppression. Targeting a protein in the skin, rather than quieting the immune system, could be a potential game changer for many patients and clinicians.
The molecule, a protein called Rac1, plays a role in wound healing. It’s also activated in the presence of streptococcal bacteria. As a result, the researchers wondered whether it could be involved in psoriasis.
Sure enough, they found that Rac1 is highly activated in psoriatic skin biopsies from patients. Activating the molecule in laboratory mice caused them to develop eerily similar skin and joint problems. Finally, blocking Rac1 activity in human psoriatic skin that had been transplanted onto mice alleviated the over proliferation of the epidermis and the recruitment of immune molecules called cytokines to the transplanted patch.
As Marinkovich explained further:
Psoriasis is one of the most prevalent skin diseases in the world. But it’s been difficult to study due to the complex interplay between genetic and environmental influences. Now we’ve learned that targeting Rac1 activation in the skin, rather than the immune system’s role in the disease, may be a way to treat the disease without needing to suppress the immune system.
Previously: My two-decade battle with psoriasis and A look at social-media use among psoriasis patients
Photo by Lew (tomswift) Holzman