Voglibose

Psoriasis is a prevalent, chronic papulosquamous skin disease, with generalized pustular psoriasis (GPP) representing a severe variant. Dysregulation of the IL-36 signaling pathway plays a crucial role in GPP, making biologics targeting this pathway the current therapeutic focus.

An elderly male patient presented with recurrent generalized erythematous, scaly patches and pustules. His medical history included GPP, psoriatic arthritis, rheumatoid arthritis, and type 2 diabetes mellitus. Previous treatments included methotrexate, glimepiride, metformin and voglibose, and adalimumab.

GPP was diagnosed based on clinical presentation, laboratory findings, and histopathological examination.

Due to inadequate response to previous treatments, spesolimab (900 mg) was administered via intravenous infusion.

Skin lesions subsided rapidly within 1 week after the initial dose. At the 6-month follow-up, the patient remained in complete clinical remission without adverse events.

This case demonstrates that spesolimab is highly effective not only for pustules in GPP but also promotes excellent regression of erythema and plaques.

Disruption of the Wnt signaling pathway (WSP), a highly conserved pathway essential for growth and organ development, has been proven to play a role in the pathogenesis of Alzheimer’s disease (AD). This study focused on repurposing the FDA-approved drug, Voglibose to target the DKK1-LRP6 site with the goal of upregulating WSP in in vitro as well as rodent model of AD. Based on our previous computational approach, Voglibose was evaluated for the DKK1 binding, neuroprotective effects were examined using SHSY5Y cells, while WSP activation was analyzed through RTPCR in the HEK293/LRP6 cell line. Rodent model of AD was developed using intracerebroventricular administration of Aβ25-35. Male Wistar rats were randomly assigned to receive oral doses of Voglibose (1 and 10 mg/kg) for 28 days, after which behavioral assessments, biochemical analyses, RT-PCR, and histopathological evaluations were conducted. Voglibose showed significant reduction in the DKK1 binding, neuroprotective property in SHSY5Y as well as activation of WSP in LRP6 overexpressed HEK293 cells. There was a significant decrease in the island latency in rats treated with lower dose (p < 0.01) and higher dose (p < 0.05) of Voglibose when compared to the disease control rats. Similarly, in the behavioral tests, Voglibose significantly improved cognition. The deposition of amyloid plaques was found to be considerably more in the disease control rats which got reduced in the treatment groups as observed in the histopathological slides stained with Congo red. Significant alterations in mRNA levels and protein expression of glycogen synthase kinase-β (GSK-3β), β-catenin (β-cat) was observed in rat brain homogenates indicating upregulation of WSP. In conclusion, Voglibose demonstrated significant neuroprotective potential in a cell line study and showed potential cognitive benefits in a rat model of AD. Furthermore, its ability to activate WSP highlights its immense potential as AD therapeutic to enhance memory and modulate key neuroprotective mechanisms.