PED1003/L27 Future Pharmacology

Question 1

How does a COX2 knockout mouse present?

Answer 1

Reduced inflammation
Significant reduction in collagen-induced arthritis

Question 2

How does spinal muscular atrophy (SMA) occur? (4)

Answer 2

Mutation in SMN1 gene
Deficiency in SMN protein leads to splicing defects in motor neurons
Loss of motor neurons in anterior horns of SC prevents signalling between brain and skeletal muscles
Progressive muscular atrophy and weakness

Question 3

How does Zolgensma work?

Answer 3

AAV9 vector enters motor neuron cells
AAV9 vector delivers SMN gene to cell nucleus
SMN gene introduced to target cells as recombinant, self-complementary DNA
Self-complementary ends form a circular episome that can persist in nucleus of non-dividing motor neuron cells
Results in rapid activation and continuous expression of SMN gene

Question 4

How are common genetic associations found? (2)

Answer 4

Twin studies
Associations at population level