Emerging treatments

Question 1

Describe the process of developing a treatment?

Answer 1

Preclinical.
Phase 1 - Health volunteers.
Phase 2 - Check therapeutic effect by testing on patients.
Phase 3 - Large scale therapeutic trials.
Approval.

Question 2

How do pharmacological chaperones work?

Answer 2

Aggregation of misfolded protein. Drug folds protein correctly.

Question 3

Disadvantage of pharmacological chaperones?

Answer 3

Mutation specific.

Question 4

What organelle degrades misfolded proteins?

Answer 4

Endoplasmic reticulum

Question 5

Example of a pharmacological modulator?

Answer 5

Receptor agonists/antagonist

Ion channel activators/blockers

Question 6

Disadvantage of pharmacological modulators?

Answer 6

Mutation specific.

Question 7

What is a non sense mutation? What does it result in?

Answer 7

Premature stop codon. Prevents protein production

Question 8

What drugs are stop codon readthrough drugs based on?

Answer 8

Aminoglycoside antibiotics as they bind to ribosome and cause mistranslation.

Question 9

Stop codon readthrough drugs disadvantage?

Answer 9

Mutation specific.

Question 10

How does mitochondrial disease therapy work?

Answer 10

IVF. Take DNA from fertilised patient egg and transfer to donor egg. Mutant mitochondrial DNA replaced with non mutant.

Question 11

What are two ways in which antisense oligonucleotides can work?

Answer 11

Blocks translation by binding to mRNA’s causing them to be destroyed. Skipping of exons.

Question 12

When does exon skipping work?

Answer 12

In large proteins.

Question 13

How does RNAi work?

Answer 13

Cleaves mRNA.

Question 14

How can virus gene therapy treat a deficiency of immune cells?

Answer 14

HSC’s harvested. Viruses infects cell. Cells are grown. Mutant HSC’s in bone marrow are killed and new HSC’S are implanted.

Question 15

Treatment for mutation that results in protein not folding properly?

Answer 15

Pharmacological chaperones.

Question 16

Treatment for mutation that results in reduce activity of the enzyme?

Answer 16

Activator

Question 17

Treatment for autosomal dominant disease caused by a point mutation?

Answer 17

Knockdown (antisense) approach.

Question 18

Treatment for autosomal dominant disease caused by a mis-sense mutation?

Answer 18

Knockdown (antisense) approach.

Question 19

Treatment for nonsense mutation caused by the change of a single nucleotide.

Answer 19

Stop codon read through

Question 20

Treatment for nonsense mutation caused by deletion that has occured in a large protein?

Answer 20

Exon skipping.

Question 21

Treatment for mutation affecting hematopoietic cells?

Answer 21

Ex vivo gene therapy.

Question 22

Types of knockdown (antisense) approach?

Answer 22

antisense oligonucleotides (ASOs) and RNA interference (RNAi)