PHDs as therapeutic targets

Question 1

What is the family of drugs that inhibit PHDs?

Answer 1

PHIs e.g. Roxadusat (anemia)

Question 2

How is Roxadustat administered?

Answer 2

Oral

Question 3

Where is EPO produced?

Answer 3

Kidneys

Question 4

How will drugs targeting the HIF response help treat ischemia?

Answer 4

Decrease in O2 supply to tissue -> boost adaptive response -> promote tissue healing

Question 5

What is IBD?

Answer 5

Inflammatory bowel disease (IBD) is a term for two conditions (Crohn’s disease and ulcerative colitis) that are characterized by chronic inflammation of the gastrointestinal (GI) tract. Prolonged inflammation results in damage to the GI tract.

Question 6

What happens to the intestinal epithelium in IBD?

Answer 6

Compromised and leaks fecal matter and bacteria into tissue
Triggers immune response

Question 7

Which section of the inflamed human intestine in IBD hypoxic?

Answer 7

Colonic mucosa

Question 8

What causes the hypoxia in inflammed colon tissue?

Answer 8

Immune cells use a lot of energy eg neutrophils (make ROS to kill bacteria) AKA high o2 consumption -> low O2 levels

Question 9

Is PHD inhibition protective in experimental colitis?

Answer 9

Yes

Question 10

How are PHIs effective in IBD?

Answer 10

Increase in epithelial cell survival to allow for an intact barrier

Question 11

What is combined with PHI in IBD?

Answer 11

Immune suppression drug e.g. cyclosporine

Question 12

How does HIF maintain the intestinal epithelium?

Answer 12

Inhibits apoptosis by regulating BNIP3 (lowers)

Question 13

What is BNIP3?

Answer 13

Induces cell death