New Approaches to Drug Treatment of Alzheimer’s disease

Symptomatic drugs

 A few new symptomatic drugs are being developed – mainly 5HT6 receptor antagonists – none yet available 

New approaches – disease modifying agents

Amyloid beta depleting methods – vaccines and passive immunisation – monoclonal antibodies [mAB] (eg. aducamumab, solanezumab, bapineuzumab, crenezumab), and eluting agents

Agents that prevent amyloid beta accumulation (beta-site amyloid precursor protein cleaving enzyme inhibitor – BACE inhibitors), or the amyloid beta oligomer’s toxic action on synapses (eg. CT1812 CogRx)

Tau depleting agents – agents that prevent tau accumulation, or inhibit tau aggregation (eg. TAI – LMTX – modified methylene blue), or tau and P-tau depleting agents – passive immunisation – monoclonal antibodies 

Anti-inflammatory agents (anti-Tumour Necrosis Factor eg. etanercept, masitinib – sigmoid1mu-receptor action)

Microglial activators


 Monoclonal antibody derived from B cells of ‘super-elderly’ individuals

Targets aggregated forms of amyloid beta and soluble oligomers and insoluble fibrils in the amyloid plaque

Study tested four doses of monthly infusions of aducamumab versus placebo over 54 weeks in 165 PET scan amyloid positive subjects with prodromal or mild Alzheimer’s disease

Results showed a dose-dependent reduction of PET amyloid burden, and a dose-dependent improvement in cognitive function (MMSE and Clinical Dementia Rating [CDR])

Drop-out rates were high – 17-38% in active treatment and 25% in placebo groups

Most common adverse event (usually asymptomatic) was Amyloid-related imaging abnormalities (ARIAs) – mainly vasogenic edema

Results prompted FDA ‘fast-track’ approval for a much larger study

Tau aggregation inhibitors (TAIs) – Methylthioninium (LMTX)

Placebo controlled study of two doses of LMTX over 60 weeks in 891 subjects with mild and moderate Alzheimer’s disease

Either as add-on to usual anti-dementia drug therapy (majority of subjects), or as mono-therapy (minority of subjects)

No benefit as an add-on drug

Clear benefit as a mono-therapy on slowing decline in ADAS-cog and ADAS-ADL scores

Slower rate of progression of brain atrophy as measured by size of lateral ventricles on MRI scan

Safety profile benign

No difference in ARIAs between active and placebo groups

A follow-up study on 220 subjects with behavioural version of Fronto-Temporal Dementia (bv-FTD) did not show any benefit

We await further Alzheimer’s disease trails

Clinical Trial Unit Griffith University Southport studies 

Steadfast study

50 plus age

MMSE 21-26

RAGE inhibitor tablet

Receptor for advanced glycation endproducts – reduce oxidative stress and inflammation

21 months duration

CogRx study

55-85 age

MMSE 18-26

CT1812 Sigma-2 antagonist tablet

Stops binding of Abeta to neurones

LP and MRI

1 month duration

Amaranth study

55-85 age

MMSE 20-30


CDR 0.5

BACE inhibitor tablet

Stops production of Abeta oligomers

MRI, PET Abeta, PET tau

2 years duration

Abbvie study

55-85 age

MMSE 22-30


CDR 0.5

Monoclonal antibody against tau

IV infusion 30-90 minutes monthly

2 years duration

MRI, PET Abeta, PET tau

To enquire about these trials and suitability of subjects contact Prof Philip Morris on +61 (0)422545753.