SERCA gene therapy

Question 1

How was SERCA action increased?

Answer 1

Over-expression
AAV9.SERCA2a injection

Disinhibition
Ad.PLB-antisense

Question 2

Benefits

Answer 2

• Anti-arrhythmic

- Positive inotropy

Question 3

Ca Sparks

Answer 3

• SR is more loaded with Ca
• But buffering Ca release decreases average spark magnitude
• SR leak:load ratio is decreased
• Large, long-lasting (most problematic) sparks are decreased the most

Question 4

Advantages of gene therapy for SERCA

Answer 4

• May evade biological regulation of SERCA (miRNA-25)