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Could Defective Stem Cells Be The Cause of Psoriasis?

December 20, 2019

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December 20, 2019 – If you watch CNN morning news programming the advertising tends to be dominated by insurance and healthcare products. I have often remarked to my wife that, based on the ads being aired, that most American watchers must be suffering from psoriasis. It seems that this chronic condition associated with the phrase “the heartbreak of psoriasis,” is worthy of Big Pharma’s attentions.

What is psoriasis?

Described as a common skin condition, psoriasis produces a rapid build-up of cells on the skin surface causing scaling and red patches which can itch, cause pain, and even become infected. Described on the Mayo Clinic site as having no cure, the pharmaceutical industry has largely focused on controlling the condition through the application of moisturizers. Some physicians attempt to treat psoriasis by trying to inhibit a patient’s stressors associating the condition with lifestyle challenges.

What makes psoriasis so frustrating is that the condition seems to be growing. In the 1970s the number of cases per 100,000 in the United States was around 50. By the late 1990s that number had doubled. And today psoriasis affects 100 million globally and in the U.S. alone costs more than $10 billion annually.

Psoriasis comes in many forms including:

Plaque psoriasis – the most common form that causes skin lesions and scaling
Nail psoriasis – affecting finger and toenails
Guttate psoriasis – often triggered by bacterial infections in young people leading to skin lesions
Inverse psoriasis – attacking sensitive areas of the body like the groin, armpits, and under the breast
Pustular psoriasis – causing blisters and pustules, and sometimes fever, chills and diarrhea
Erythrodermic psoriasis – the rarest and one that can cover an entire body with a red, peeling rash
Psoriatic arthritis – causing painful joints as well as the normal scaling and skin eruptions

The common belief in the causes of these different manifestations is a compromised immune system in which the body’s white blood cells including T cells and neutrophils turn on healthy skin cells attacking them as if they were a foreign invader. That’s why doctors look for a trigger that leads to the onset of the condition: psoriasis occurring after a strep throat infection, or after a cut or scrape, insect bite, or severe sunburn, as examples. Psoriasis may be triggered by a vitamin D deficiency, or by smoking, alcohol consumption, or medications. And psoriasis is associated with greater occurrences of Type 2 diabetes, celiac, Crohn’s and other inflammatory bowel diseases.

More treatments are needed for the 100 million individuals worldwide affected by psoriasis. Researchers from Brigham and Women’s Hospital and the Harvard Stem Cell Institute have discovered a possible source of the skin thickening that may be triggered by dysregulated stem cells.

But new research being done at Brigham and Women’s Hospital and the Harvard Stem Cell Institute in Boston may have discovered the source for the condition which may soon lead to new treatments of the condition. Publishing in the Journal of Investigative Dermatology, senior author, George Murphy, Director of the Program in Dermatopathology, Department of Pathology, at Brigham, describes a dysregulated defective stem cell as a likely disease trigger.

States Murphy, “Psoriasis places social and psychological stress on patients and is associated with risk of diabetes, cardiovascular disease and more. While steroids and biologics can be prescribed, we don’t have a cure because we haven’t understood the cause,” that is until now. Murphy goes on to describe a dysregulated stem cell and its progeny as the skin-thickening agent that leads to psoriasis.

Murphy’s co-senior author, Christine Lian, also at Brigham, describes the team’s pursuit of an underlying cause looking at potential epigenetic abnormalities. And what they discovered was a defect in the epigenetic covering in stem cells resulting in the loss of a DNA methylation hydroxymethylation mark. Given the name, 5-hmC, the defect could be seen in psoriasis cells but not in other thickened skin cells such as callous. The team, in focusing on 5-hmC, was able to replicate psoriasis in mouse studies. It is their belief based on these studies that restoring 5-hmC levels to normal will correct the deficiency that leads to psoriasis. Vitamin C supplements may help since in previous investigations at Brigham and Women’s, 5-hmC loss was seen to be restored to normal levels through additional amounts of ascorbic acid being added to the diet.

The Brigham researchers believe that their discovery could transform the treatment of psoriasis with Murphy concluding that it may lead to “more personalized and targeted approaches directed at the very cells that accumulate to form the heartbreak of this all-too-often devastating skin condition.”