Novel treatment for AD

Question 1

describe how efficacy is measured

Answer 1

1. pharmacokinetics
2. measurement of suitable biomarker changes in phase II clinical trials
   - eg. measuring changes in cerebrospinal fluid biomarkers
3. changes to cognition

Question 2

describe the drugs targeting amyloid B

Answer 2

1. amyloid beta generation
   - beta secretase/gamma secretase (solanezumab)
   - tarenflurbil
   - latrepirdine
   - semagacestat
2. immune therapy- fragments of the AB protein
   - effective in mouse models and decrease AB plaques in humans
   - bapineuzumab and solanezumab

Question 3

what are the 2 types of kinase target Tau

Answer 3

1. proline
   - GSK3-B
   - CDK5
   - ERK1/2
2. non proline
   - microtubule affinity regulating kinase
   - PKA

Question 4

what are GLP1 analogues

Answer 4

1. diabetes and AD risk
2. insulin aids neuronal growth
3. GLP1 analogues- reduce intracellular APP and AB
4. decrease AB plaques in 3xTg-AD mice
5. liraglutide- decrease AB, reduce synapse loss and improved cognition

Question 5

what affects the ageing process

Answer 5

1. single gene mutations affect ageing
   - I/IGF-1 signalling
   - mTOR (mammalian target of rapamycin): cell growth and proliferation, protein synthesis and regulation of autophagy
   - sirtuins

Question 6

what is the effect of rapamycin

Answer 6

• restores mTOR signalling and reduces AB deposition
• decreases AB pathology by inducing autophagy
• also reduces impairment to learning and memory