In the News

Question 1

Alzheimer’s

Answer 1

• Most common NDD
• Age biggest risk factor - ageing population
• AChE inhibitors – donepezil, rivastigmine, galantamine – 40-70% mild to moderate AD show temporary relief symptoms (6-12 m.)
• NMDAR antagonist memantine can slow progression in moderate to severe AD
• Limited effects, unwanted side effects

Question 2

Nucleus basalis of Meynert- in AD

Answer 2

loss of neurons in this area

Question 3

Testing amyloid hypothesis

Answer 3

• Aducanumab (Biogen) – high-affinity, fully human IgG1 monoclonal antibody vs. conformational epitope found on Aβ; binds aggregated forms of Aβ, not monomer

Question 4

Testing amyloid hypothesis Solanezumab

Answer 4

(Eli Lilly) - humanized monoclonal (doesn’t elicit an immune response in humans) IgG1 antibody vs. mid-domain of Aβ peptide - recognizes soluble monomeric, not fibrillar, Aβ

Question 5

Testing amyloid hypothesis - • Verubecestat (Merck)

Answer 5

small-molecule inhibitor of BACE1 and BACE2

Question 6

Aducanumab

Answer 6

• Data showing amyloid loss is positive
• But sceptical in relation to cognitive issues
  PET scan – illustrates advances with diagnostics
  Penetration shown in transgenic mice using horseradish peroxidase
  Targets amyloid plaques and recruit microglia to alleviate burden

Phase 3 trial – ENGAGE AND EMERGE
1 of 2 doses or placebo over 18 months
Looking at cognitive function improvement