Parsaclisib Shows Promise in Easing Sjögren’s Symptoms in Mouse Models
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The findings of a new study support the development of Incyte‘s parsaclisib as a potential therapy for Sjögren’s syndrome and other autoimmune diseases.
Parsaclisib, an oral inhibitor of phosphatidylinositol 3-kinase (PI3K) delta, was found to ease the symptoms of Sjögren’s and other disorders in a study using mouse models.
That study, “The PI3Kδ inhibitor parsaclisib ameliorates pathology and reduces autoantibody formation in preclinical models of systemic lupus erythematosus and Sjӧgren’s syndrome,” was published in International Immunopharmacology. It was funded by Incyte.
PI3K delta is a protein that’s involved in the activation of certain immune cells, particularly B-cells. As such, blocking PI3K delta activity has emerged as a potential strategy to lessen inflammation in autoimmune diseases like Sjögren’s syndrome, where the immune system attacks the body’s own tissues, particularly the glands that make tears and saliva.
Incyte is developing parsaclisib (INCB050465) as an oral inhibitor of PI3K delta to potentially treat several indications. The company is currently running clinical trials of parsaclisib in various blood cancers and immune disorders.
Now, researchers at Incyte evaluated parsaclisib in two mouse models of Sjögren’s, and also tested the medication in three models of another autoimmune disease called systemic lupus erythematosus or SLE.
“In this study, we aimed to characterize the capability of parsaclisib to ameliorate disease progression and phenotype in [mouse] models of SLE and Sjögren’s syndrome,” the researchers wrote.
In the Sjögren’s models, treatment with parsaclisib significantly improved salivary gland pathology. That means that treated mice had less evidence of salivary gland damage compared with untreated mice.
Parsaclisib treatment also significantly reduced the production of autoantibodies, or self-targeting antibodies, which are proteins produced by B-cells that help to drive inflammation in autoimmune diseases.
Additionally, the medication significantly reduced levels of B-cell activating factor or BAFF in the mice’s saliva and salivary glands. As its name implies, BAFF is a signaling protein that prompts B-cells to activate and become more inflammatory.
Treatment with parsaclisib also reduced a marker of PI3K delta activation — namely phosphorylated protein kinase B (AKT) — which is consistent with the medication’s known mechanism of action.
In the mouse models of SLE, parsaclisib also showed benefits, leading to reduced markers of inflammation and of kidney damage.
“The results from our … studies underscore the role for [PI3K delta] pathway inhibition in normalizing the number of autoreactive B-cells and decreasing autoantibody levels, which can lead to lupus [and Sjögren’s] symptom improvement,” the researchers wrote.
“Overall, our findings provide a mechanistic rationale for [PI3K delta] inhibition as a potential therapeutic strategy for treatment of B-cell-mediated, antibody-driven autoimmune diseases,” they concluded.
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