New research suggests a common skin disease with no cure could be treated with nutritional supplements.
The B vitamin derivative showed "encouraging" results for reducing psoriasis symptoms in studies with both humans and mice.
Psoriasis causes a rash with itchy, scaly patches, most often on the knees, elbows, and around the waist—and the autoimmune condition has no cure.
Now researchers in China have discovered that the vitamin B5 derivative called pantethine limits the activity of immune cells that are key contributors to autoimmune diseases such as psoriasis.
Their findings, published in the Journal of Experimental Medicine (JEM), show that pantethine helped alleviate the symptoms of psoriasis in a small human trial—and also entirely prevented its development \in mice.
The Beijing team explained that dendritic cells are specialized immune cells that help to coordinate the different parts of the immune system.
They can engulf and present foreign antigens to activate highly-specific T-cells, as well as secrete a range of immune signaling molecules to recruit other types of immune cells, promoting inflammation.
Because of their central role in directing immune responses, aberrant activation of dendritic cells is believed to underlie several autoimmune diseases, including psoriasis. But strategies around inflammatory diseases remain under-explored, says study co-lead author Dr. Wei-Na Zhang.
"Metabolic pathways and their associated metabolites play vital roles in regulating immune cell function and autoimmune progression.
The levels of metabolic enzymes known as Vanins are elevated in the dendritic cells of patients with psoriasis and several other autoimmune diseases.
If you can deplete those enzymes, you can inhibit dendritic cell activation and limit their ability to activate T-cells. (In fact, treating mice with a drug that inhibits Vanins prevented the animals from developing psoriasis.)
Pantethine is a widely available nutritional supplement often used to lower cholesterol levels due to its ability to inhibit cholesterol synthesis.
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Dr. Zhang said Vanin enzymes convert the metabolite pantethine into vitamin B5, an essential nutrient required for cellular energy production.
His team at the State Key Laboratory of Biomedical Analysis said cholesterol had previously been shown to promote the activation of dendritic cells, and high blood cholesterol is a 'major risk factor for the development of psoriasis'.
They determined that increased Vanin activity in dendritic cells reduces panthetine levels, leading to increased cholesterol synthesis and dendritic cell hyperactivation.
Replenishing pantethine levels reversed the process, lowering the accumulation of cholesterol and suppressing dendritic cell activation.
"Insufficient pantethine levels may be the crucial contributor to hyperactivation of dendritic cells, and autoimmune inflammation following the up-regulation of Vanins," said Zhang.
The small 'proof-of-concept' trial treated 24 psoriasis patients with ointment, but half of the patients also received pantethine tablets.
Over the course of 12 weeks, patients given the additional pantethine treatment showed improved symptoms, particularly if they had elevated blood cholesterol levels to begin with.
"Our investigator-initiated clinical trial demonstrated encouraging therapeutic efficacy of pantethine as an adjunctive therapy in psoriasis, providing a foundation for therapeutic strategies targeting dendritic-mediated autoimmune diseases."
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