Treatments of Neurodegenerative Diseases

Question 1

Which aggregate to target?

Answer 1

Oligomer
Bigger than monomer and dimer, but not large aggregate
We think these are the most toxic, because they can get around

Question 2

Current strategies for dealing with aggregates

Answer 2

Stop formation
Increase breakdown

Question 3

Stop formation of aggregates

Answer 3

• Target parent protein: antisense, genetic KO (CrispR/Cas9)
• Alter metabolism: stimulate breakdown enzymes
• Prevent misfolding: beta-sheet breakers: chaperones

Question 4

Increase breakdown of aggregates

Answer 4

• Stimulate natural systems eg UPS or autophogy
• Target the aggregates: antibodies

Question 5

Anti-sense RNA for Huntington’s disease

Answer 5

AS RNA (ASO) reduced the presence of the mutant that causes Huntington’s by 50% in preclinical studies

Question 6

Gamma secretase inhibitors for Alzheimer’s

Answer 6

Should have blocked Aβ aggregations
Actually showed worsening of symptoms
Failure

Question 7

Antibodies to Aβ for Alzheimer’s

Answer 7

Antibodies against Aβ reduce plaque load and cognitive decline by 20-40%
Delivered through cannula infusion
“Believed” to act through recruitment of microglia
Side-effects quite severe (brain haemorrhaging)
Overall effects of these drugs considered “minimal”

Question 8

What drives reuptake of dopamine?

Answer 8

Dopamine transporter (DAT)

Question 9

What drives PS Cell Uptake?

Answer 9

Dopamine Receptors (DR)

Question 10

Enzymes involved in synthesis of dopamine

Answer 10

Tyrosine Hydroxylase

Question 11

Early detection of NDs

Answer 11

Reversal is almost impossible, so we have to stop it early
Requires large scale screening
Has to be detectible in blood/urine or non-invasive

Question 12

Research into stem cells

Answer 12

There’s a lot of it
A bit far-fetched due to demands on of cost and time
Meaningless without treatment