TABLE 7.

Clinical trials and clinical applications of experimental approaches to increase ABCC5 expression.

Experimental approach	Clinical trials and applications
Dexamethasonea	Multiple sclerosis; allergies; cerebral edema; inflammation; shock; COVID-19; asthma; atopic dermatitis; contact dermatitis; chemotherapy-induced nausea and vomiting; altitude sickness; tumor metastasis-related spinal cord compression (Teachey and Pui, 2019; Johnson et al., 2023); rheumatic diseases; pemphigus; severe erythema multiforme (Stevens-Johnson syndrome); exfoliative dermatitis; bullous dermatitis herpetiformis; severe seborrheic dermatitis; severe psoriasis; flare-ups ulcerative colitis, multiple sclerosis, myasthenia gravis (Medical News Today, 2022)
Increased expression of FOXM1b	No human applications found

^aDexamethasone is a glucocorticoid used clinically to prevent and reduce inflammation. Although inflammatory mechanisms are increased in AD brain (Kinney et al., 2018; Kiraly et al., 2023), clinical trials with anti-inflammatory agents found no evidence for slowing of AD clinical progression (Aisen et al., 2000, 2003). Chronic treatment with dexamethasone was found to damage hippocampal neurons in vitro (Zhang et al., 2017) and in vivo (Hu et al., 2016), and dexamethasone administration increased tau phosphorylation in 3×Tg and Tg2576 mice (Joshi et al., 2012, 2013). A later study with 3×Tg mice found that treatment with dexamethasone exacerbated both Aβ and tau pathology (Green et al., 2006).

^bIncreasing FOXM1 to increase ABCC5 expression in AD patients may be contraindicated, based on a study of FOXM1 staining in 236 patients with breast cancer (Ahn et al., 2015). Increased FOXM1 immunoreactivity correlated with adverse clinicopathological features including larger size of tumors, metastasis to lymph nodes, and advanced tumor stage. ABCC5, ATP binding cassette subfamily C member 5; AD, Alzheimer’s disease; COVID19, coronavirus disease 2019; FOXM1, forkhead box M1.