Table 1.

Outcomes of IN DFO Treatment in Animal Models of AD at Various Doses and Dosing Intervals

source	animal model	formulation	dose administered	dose detected in brain	outcome
Guo etal.48	male APP/PS1 double transgenic mice watered with high-dose	IN saline solution	200 mg/kg bodyweight once every other day for 90 days		reduced expression and phosphorylation of APP protein; attenuated Aβ burden; improved memory retention
Fine etal.49	male APP/PS1 amyloid mice	10% DFO solution in 0.2X phosphate buffered saline (PBS) at pH 6.0 delivered IN	3X/week with 0.24C for 18 weeks from 36 to 54 weeks of age; dosing was continued through 4 weeks of behavioral testing beginning at week 54		decreased loss of reference and working memory in Morris and radial arm water mazes; decreased soluble Aβ40 and Aβ42 in cortex and hippocampus; decreased oxidative stress; decreased GSK3β activity
Guo etal.50	male APP/PS1 double transgenic mice	IN saline solution	200 mg/kg bodyweight once every other day for 90 days		decreased induced tau phosphorylation; decreases Fe-induced CDK5 activity and GSK3β activity
Guo etal.51	male APP/PS1 double transgenic mice	saline solution delivered IN	200 mg/kg once every other day for 3 months beginning at 6 months of age		decreased Aβ deposition; rescued synapse loss; upregulated HIF-la mRNA and protein, induced TFR, DMT1, and BDNF; decrease in iron in the hippocampus; enhanced phosphorylation of (MAPK)/P38 kinase
Fine etal.55	P301L transgenic tau mice	10% solution in 0.2X PBS at pH 6.0 delivered IN	2.4 mg 3X/week starting at 11 weeks of age; behavioral testing began at 32 weeks, and IN DFO treatment was continued through 5 weeks of behavioral testing		improved performance in radial arm water maze test when compared to untreated transgenic mice; increased pGSK3β and HIF-la in transgenic mice
Fine etal.56	male ICV STZ rat model (nonamyloid/ tau model)	10% solution in 0.2X PBS at pH 6.0 delivered IN	3 mg 3X/week for 4 weeks postsurgery; behavioral tests began at 4 weeks, and dosing was continued through such experiments; selected groups were pretreated with DFO for 4 days prior to surgery		ICV STZ rats treated with IN DFO both before and after surgery had shorter escape latencies in Morris water maze behavioral tests; pretreatment with IN DFO decreased foot slips on tapered balance beam test; IN DFO treatment decreased oxidation and increased insulin receptor expression
Hanson etal.57	male C57 mice for radiolabeled pharmacokinetic studies; male APP/PS1 mice	10% solution in 0.2X PBS at pH 6.0	2.4 mg 3X/week for 4 weeks beginning at 36 weeks of age	0.4–29 μM after 30 min	reduced escape latencies in Morris water maze; reduced brain levels of aluminum; no change in amyloid plaque deposition