BioMed Research International / 2014 / Article / Tab 3

Review Article

Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials

Table 3

Other novel approaches in AD clinical trials.

MechanismRCTStatusEstimated endDementia stageEnrollmentDurationReported outcomesDetails of drugs/RCTS

Anti-inflammation and antioxidationCurcuminPhase 2; completed2007.12Mild-to-moderate33NSAID, cholesterol-lowering properties
EtanerceptPhase 1; ongoing2015.6Mild-to-moderate1212 months↑cognitive function with other nutrients.Approved drug for arthritis; may modulate immune system; benefit AD patients
dl-alpha-tocopherol (vitamin E)Phase 3; completed2012.10Mild-to-moderate613
PUFAPhase 1/2; ongoing*2015.110018 monthsTested alone or together with lipoic acid
RO4602522Phase 1; completed2013.517

PDE inhibitorsPF-04447943Phase 2, completed2010.9Mild-to-moderate198Selective PDE 9A inhibitor
MK0952Phase 2; completed2007.11Mild-to-moderateSelective PDE 4 inhibitor
CilostazolPhase 4; completed2013.7Mild-to-moderate46PDE3 inhibitor, Antiplatelet agent in WMHI; ↑pCREB

Tyrosine kinase inhibitorMasitinibPhase 3; ongoing*2015.12Mild-to-moderate396In combination with AChEI and/or memantine

Insulin and GLP1-R agonistsIntranasal insulin (glulisine)Phase 2/3; ongoing2015.2MCI/mild AD24012 months
Exendin-4 (exenatide)Phase 2; ongoing2016.7MCI/early stage1003 yearsShowed neuroprotectionDiabetes agent
LiraglutidePhase 2; ongoing2017.1early stage20612 months

Modulating mitochondrial functionAC-1204Phase 2/3; ongoing2015.1Mild-to-moderate48026 weeks
Latrepirdine (Dimebon)Phase 3; completed2009.12Mild-to-moderate5986 months

RXR agonistBexarotenePhase 2; ongoing2014.3Mild-to-moderate20Approved anticancer drug; linked to key pathways relevant to AD and Aβ

NGF deliveryCERE-110Phase 2; ongoing2014.12Mild-to-moderate5024 months24 monthsDesigned to help neurons function better; uses a virus to transfer NGF gene
Encapsulated Cell biodelivery of NGFPhase 1b2011.12612 months

RCT: randomized controlled trial; NSAID: nonsteroidal anti-inflammatory drugs; PDE: phosphodiesterase; WMHI: subcortical vascular disease; pCREB: phosphorylated cAMP-response element binding protein; AChEI: acetylcholinesterase inhibitor; GLP1-R: glucagon-likepeptide1 receptor; MCI: mild cognitive impairment; RXR: retinoid X receptors; NGF: nerve growth factor.
*RCTs with a combination of another drug.
Data sources: http://www.clinicaltrials.gov/.