Table 3. Targeted therapies for intracranial aneurysms (IAs).
| Agent | Model | Efficacy |
|---|---|---|
| Nuclear factor-κ B decoy ODN (Aoki et al, 2007c) | IA was induced in rats with administration of nuclear factor-κ B decoy ODN (n=10) or scrambled decoy ODN (control, n=10) | Significant decrease in incidence of aneurysmal changes and aneurysm size when given at early stage of aneurysm formation |
| Statins (Marbacher et al, 2011) | Human. 300 cases of IA (265 with ruptured IA, 64.3% were female, 68.4% were ⩾50 years) and 900 matched controls (64.3% were women, 68.5% were ⩾50 years) | Cases and controls were similar with respect to statin intake (10.0% and 10.7%, respectively) |
| Simvastatin (Aoki et al, 2008b) | IA was induced in rats with (n=11) or without (n=10) administration of simvastatin | Significant increase in media thickness and reduction in IA size. Inhibition of IA enlargement and thinning of the media of preexisting IA |
| Simvastatin (Tada et al, 2011) | IA induced in rats with (n=13) or without (n=8) administration of simvastatin (5 mg/kg per day) | Higher incidence of IA in simvastatin-treated rats |
| Pravastatin (Tada et al, 2011) | IA induced in rats with or without (n=8) administration of pravastatin (5, 25, and 50 mg/kg per day, n=12 each) | - Inhibits IA formation at 5 mg/kg per day (but negligible effect compared with control) - Induces IA formation and possibly IA rupture at high dose (25 and 50 mg/kg per day) |
| Pravastatin (Kimura et al, 2010) | IA induced in rats with or without (n=14) administration of low (50 mg/kg per day, n=10) and high dose (100 mg/kg per day, n=12) pravastatin | Reduced formation of IA (50% in control, 10% in low dose, and 8% in high dose group) |
| Pitavastatin (Aoki et al, 2009a) | IA induced in rats with (n=10) or without (n=10) administration of pitavastatin (4 mg/kg per day) | Significant decrease in IA size and IEL score, and increase in media thickness. Media thickening in preexisting IA |
| Aspirin (Hasan et al, 2011) | Human. 271 nested case–control patients with untreated IA (58 cases, i.e., sustained an SAH, and 213 control). 74% were women, mean age 57 years | Significantly lower odds of hemorrhage in patients using aspirin three times weekly to daily |
| MMP inhibitor (Tolylsam) (Aoki et al, 2007a) | IA induced in rats with (n=10) or without (n=21) administration of tolylsam | Significant decrease in incidence of advanced IA (90% in control and 50% in treated group) |
| MCP1 inhibitor (7ND) (Aoki et al, 2009b) | IA induced in rats with (n=8) or without (n=8) administration of 7ND | Significant decrease in aneurysm size |
| Phosphodiesterase-4 inhibitor (Ibudilast) (Yagi et al, 2010) | IA induced in rats with or without (n=20) administration of 30 mg/kg (n=15) and 60 mg/kg (n=15) of ibudilast | Significant decrease in aneurysmal stage only with 60 mg/kg |
| Cathepsin inhibitor (NC-2300) (Aoki et al, 2008c) | IA induced in rats with (n=10) or without (n=21) administration of cathepsin inhibitor | Significant decrease in incidence of advanced IA (90% in control and 50% in treated group) |
| ARB (Olmesartan) (Kimura et al, 2010) | IA induced in rats with or without (n=14) administration of low (3 mg/kg per day, n=13) and high dose (10 mg/kg per day, n=12) olmesartan | Reduced formation of IA (50% in control, 8% in low dose, and 0% in high dose group—but mainly via blood pressure reduction) |
| ARB (Valsartan) (Aoki et al, 2009d) | IA induced in rats with (n=10) or without (n=10) administration of valsartan | No change in IEL score, IA size, and media thickness |
| ARB (Candesartan) (Tamura et al, 2009) | IA induced in rats with (n=16) or without (n=18) administration of candesartan | Significant decrease in IA formation but mainly via blood pressure reduction |
| Mast cell degranulation inhibitor (Tranilast, emedastine difumarate) (Ishibashi et al, 2010) | IA induced in rats with or without administration of mast cell degranulation inhibitor | Decrease in IA size and increase in media thickness |
| Free radical scavenger (Edaravone) (Aoki et al, 2009e) | IA induced in rats with (n=10) or without (n=21) administration of edaravone | Significant decrease in IA size, IEL score, and increase in media thickness |
ODN, oligodeoxynucleotide; ARB, angiotensin-II receptor blocker; IEL, internal elastic lamina; MCP1, monocyte chemoattractant protein 1; SAH, subarachnoid hemorrhage.