Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials
Table 2
RCTs targeting neurotransmitter systems in recent years.
Mechanism
RCT
Status
Estimated end
Dementia stage
Enrollment
Duration
Reported outcomes
Details of drugs/RCTS
Cholinergic agents
AchE inhibitor
Huperzine A
Phase 2/3; completed
2012.6
Mild-to-moderate
390
6 months
↑cognitive function, daily living activity, global clinical assessment
A natural AChEI; antioxidant and neuroprotective properties [215]
Ladostigil hemitartrate
Phase 2; ongoing
2016.9
MCI
200
36 months
Antioxidant properties; modulates APP processing
Nicotinic receptor agonist
EVP-6124
Phase 3; ongoing
2017.7
Mild-to-moderate
790
26 weeks
Positive outcomes in a 24-week phase 2b RCT
RO5313534
Phase 2; completed
2010.11
Mild-to-moderate
389
6 months
α7 nicotinic receptor agonist; as add-on therapy to donepezil
Ispronicline (AZD3480)
Phase 2; ongoing
2014.7
Mild-to-moderate
300
1 year
α4β2 and α2β2 nicotinic receptor agonist
MT-4666
Phase 2; ongoing
2015.5
Mild-to-moderate
450
24 weeks
ABT-089
Phase 2; terminated
2013.10
Mild-to-moderate
434
24 weeks
MK-7622
Phase 2b; ongoing
2017.8
Mild-to-moderate
830
12–24 weeks
As adjunctive therapy to donepezil
α7 receptor modulator
Glutamatergic agents
AVP-923
Phase 2; ongoing
2014.9
Mild-to-moderate
200
10 weeks
Behavioral problems
NMDA receptor antagonist
Serotoninergic agents
Lu AE58054
Phase 3; ongoing*
2016.1
Mild-to-moderate
≈2500
Positive results in a phase 2 RCT, 278 participants, 6 months;
Several phase3 RCTS with donepezil (AchEI);
SB-742457
Phase 2; completed
2011.8
Mild-to-moderate
684
6 months
showed positive results
RCT: randomized controlled trial; AChEI: acetylcholinesterase inhibitor; MCI: mild cognitive impairment; NMDA: N-methyl-D-aspartic acid. Data sources: http://www.clinicaltrials.gov/.
*RCTs with a combination of another drug.
