Vitamin Derivative Pantethine Alleviates Psoriasis Symptoms in Small Human Trial

Researchers headed by a team at State Key Laboratory of Biomedical Analysis (SKLBA) (formerly known as National Center of Biomedical Analysis) in Beijing have discovered that the vitamin B5 derivative pantethine limits the activity of dendritic cells (DCs), which are immune cells that are key contributors to autoimmune diseases such as psoriasis. The newly reported study showed that pantethine prevented the development of psoriasis in mice, and in a small-scale trial in human psoriasis patients administering pantethine in combination with topical calcipotriol/betamethasone dipropionate helped to alleviate symptoms.

In their published study in Journal of Experimental Medicine (JEM) (“Vanin-pantethine metabolic axis shapes dendritic cell function and affects inflammatory disorder progression,”) senior author Wei-Na Zhang, PhD, a researcher at the State Key Laboratory of Biomedical Analysis, and colleagues, suggested that their findings point to “… a potentially viable metabolic strategy for DC-centered intervention in AIDs [autoimmune diseases].” Zhang co-led the new JEM study with Qing Xia PhD, Ai-Ling Li, PhD, and Tao Zhou, PhD, also from the State Key Laboratory of Biomedical Analysis, and Cheng-Xin Li, PhD, from The First Medical Center of Chinese PLA General Hospital in Beijing.

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 variety of immune signaling molecules to recruit other types of immune cells and promote inflammation. Because of this central role in directing immune responses, abnormal activation of dendritic cells is thought to underlie a variety of autoimmune diseases, including psoriasis. “Aberrant activation of dendritic cells (DCs) is intricately associated with inflammatory diseases, rendering DCs an appealing therapeutic target,” the authors wrote. “Metabolites are emerging as crucial regulators of DCs, yet therapeutic strategies targeting DC metabolism for inflammatory diseases remain underexplored.”

Zhang further added, “Emerging evidence highlights that metabolic pathways and their associated metabolites play vital roles in regulating immune cell function and autoimmune progression. But therapeutic strategies targeting metabolism in inflammatory diseases remain underexplored.”

Through their study the team found that levels of metabolic enzymes known as Vanins are elevated in the dendritic cells of patients with psoriasis and several other autoimmune diseases. Vanin enzymes convert the metabolite pantethine into vitamin B5, an essential nutrient required for cellular energy production. Pantethine itself is a widely available nutritional supplement often used to lower blood cholesterol levels due to its ability to inhibit cholesterol synthesis. Intriguingly, cholesterol can promote the activation of dendritic cells, and high blood cholesterol is a major risk factor for the development of psoriasis.

Through their study the team showed that depleting these enzymes inhibited dendritic cell activation and limited their ability to activate T cells. Moreover, treating mice with a drug that inhibits Vanins prevented the animals from developing psoriasis.

Zhang and colleagues determined that increased Vanin activity in dendritic cells reduces panthetine levels, leading to increased cholesterol synthesis and dendritic cell hyperactivation. Replenishing pantethine levels reversed this process, lowering the accumulation of cholesterol and suppressing dendritic cell activation. “Pantethine supplementation or pharmacologically induced Vanin inhibition reduces cholesterol overload, impedes DC activation, and mitigates psoriasiform inflammation,” they wrote.

“We found that pantethine administration effectively alleviated psoriasis in mice, suggesting that insufficient pantethine levels may be the crucial contributor to hyperactivation of dendritic cells and autoimmune inflammation following the upregulation of Vanins,” Zhang noted.

To investigate further the researchers initiated a small-scale trial of pantethine supplementation in 24 human psoriasis patients. Every patient was treated with topical calcipotriene/betamethasone ointment, but half of the patients also received oral pantethine. Over the course of 12 weeks, patients given the additional pantethine treatment showed improved symptoms, particularly if they had elevated blood cholesterol levels at the start of the trial. “Importantly, our clinical trial revealed that pantethine combination therapy significantly decelerates the progression of psoriasis in patients,” they reported.

Zhang commented, “Our investigator-initiated clinical trial demonstrated encouraging therapeutic efficacy of pantethine as an adjunctive therapy in psoriasis, but these findings should be interpreted as proof-of-concept for clinical feasibility rather than direct mechanistic validation. Overall, our study uncovers the Vanin-pantethine-cholesterol axis as a key metabolic pathway governing dendritic cell activation and provides a foundation for therapeutic strategies targeting several dendritic cell–mediated autoimmune diseases.”

The post Vitamin Derivative Pantethine Alleviates Psoriasis Symptoms in Small Human Trial appeared first on GEN - Genetic Engineering and Biotechnology News.