Review
Copyright ©The Author(s) 2015.
World J Pharmacol. Sep 9, 2015; 4(3): 236-264
Published online Sep 9, 2015. doi: 10.5497/wjp.v4.i3.236
Table 1 Novel therapeutic strategies for Alzheimer's disease management
ActiveMechanism of actionDrug delivery systemEfficacy study modelRef.
Oral
RutinAntioxidantOnly drugPreclinical rodent streptozotocin induced AD model[85]
(-)-Epigallocatechin-3-gallateAntioxidant, α-secretase activatorNanolipid carriersIn vitro, preclinical rodent model[137]
ChitosanPreclinical rodent model[138]
MifepristoneAntiprogesterone activity, AD symptomatic reliefPLGA nanoparticlesPreclinical rodent model[139-141]
EstradiolEstrogenic activity, AD symptomatic reliefTween 80 coated PLGA nanoparticlesPreclinical rodent model[142,143]
CNTF P021 (Ac-DGGLAG-NH2)Neurotrophic factorOnly drugPreclinical rodent AD transgenic model[144]
ClioquinolMetal ion Cu/Zn chelatorOnly drugPreclinical rodent AD transgenic model[145,146]
GalactoseGlucose restorationOnly drugPreclinical streptozotocin induced rodent model[147]
Transdermal
GalantamineAChEIDrug in adhesive type patchPreclinical rodent model[151]
Donepezil (base and salt form)AChEIFatty acid based topical formulationIn vitro skin model, preclinical rodent model[152]
Huperzine AAChEIMicroemulsion, solid lipid nanoparticles, nanostructured lipid carriersIn vitro skin model, preclinical rodent model[153]
DonepezilAChEIIontophoresis, Wearable Electronic Drug Delivery System patchesPreclinical rodent model[154]
Rasageline and selegilineMAO-B inhibitorsSolution and carbopol based gel - iontophoresisIn vitro skin model[155]
MemantineNMDA receptor modulatorIontophoresis with penetration enhancersIn vitro skin model[156]
(1-42) antigenAD immunovaccineMicroneedlesPreclinical rodent model[161]
Intravenous
ClioquinolCu/Zn chelatorOnly drugPreclinical rodent AD transgenic model[42]
LithiumGSK-3 inhibitor of tau phosphorylationOnly drugPreclinical rodent AD transgenic model[76,77]
Valproate sodiumGSK-3 inhibitor of tau phosphorylationOnly drugPreclinical rodent AD transgenic model[76,77]
Nerve growth factorCholinergic neuron protectionPolysorbate 80 coated PBCA nanoparticlesPreclinical scopolamine induced rodent model[162]
PEG chemical conjugatePreclinical rodent model[163]
Antitransferrin antibody chemical conjugatePreclinical rodent model[163,164]
GalantamineAChEIPeptide targeting ligand functionalized liposomesIn vitro cell line[165]
Aβ binding peptide QSHAβ reductionTargeted PEGylated polylactic acid nanocarriersPreclinical AD induced rodent model[166]
Thiflavin TSpecific Aβ plaque bindingPBCA NanoparticlesPreclinical rodent model[168,169]
Anti- Aβ antibodyAD immunotherapyOnly drugPreclinical rodent AD transgenic model[49,50]
BAM -10 antibodyAD immunotherapyExternal targeting with trans-cranial application of magnetic and ultrasound energyPreclinical rodent AD transgenic model[186,187]
Cholic acidCholinergic managementFluorescent labeled PEG-PLGA nanoparticles, external ultrasoundPreclinical rodent model[188]
Octapeptide NAP derived from the neurotrophic factorNeuroprotective activityOnly drugPreclinical rodent model[196,197]
Mesenchymal stem CellsNeuronal growthOnly drugIn vitro, Preclinical transgenic AD rodent model[203,204]
Intranasal
InsulinMulticascade anti AD activityOnly drugPreclinical rodent model[130-132]
TacrineAChEICyclodextrin coated bovine serum albumin nanospeheresEx vivo permeation model[175]
CurcuminAntioxidant, anti- Aβ activityNanoemulsionEx vivo permeation model[177]
siRNAAD associated gene silencingCell penetrating peptide TAT conjugated polycaprolactone- PEG MicellesEarly development[184]
Gene deliveryAD associated gene silencingExosomesEarly development[185]
Pituitary adenylate cyclase-activating polypeptideNeuroprotective activityOnly drugPreclinical rodent model[198]
Implants
RivastigmineAChEIBTM and SAM based organogel implants, subcutaneous administrationPreclinical rodent model[195]
Table 2 Current market status and ongoing clinical investigation for Alzheimer's disease therapeutics
ActiveMechanism of actionDrug delivery routeClinical statusRef.
Approved drugs
Tacrine (Cognex®)AChEIOralUSFDA approved[205]
Donepezil (Aricept®)AChEIOralUSFDA approved
Galantamine (Razadyne, Reminyl®)AChEIOralUSFDA approved
Rivastigmine (Exelon®)AChEITransdermal patchUSFDA approved
Memantine (Namenda, Axura®, Ebixa®)NMDA receptor inhibitor, glutaminergic system modifierOralUSFDA approved
Drugs under clinical investigation
EHT-0202α-secretase activatorOralPhase 2[29]
CTS-21166β-secretase inhibitorOralPhase 2[35]
MK-0752γ-secretase inhibitorOralPhase 2[29,36]
ImmunoglobulinAD immune activityIntravenousPhase 2[170]
Omega-3-fatty acid treatment, nutritional supplement, physical exercise and cognitive stimulationAD symptomatic managementOralPhase 3[199]
Cerebrolysin and AChEINeirotropic, AChEIOralPhase 4[200,201]
Alzhemed™Activity Aβ aggregation inhibitorOral (dietary supplement)Phase 3[206]