Table 3.
Gene Therapy Targets for Heart Failure
| Molecular Target | Stage in Development | Findings | Model Assessed | Reference |
|---|---|---|---|---|
| Sarcoendoplasmic Reticulum calcium‐ATPase 2a (SERCA2a) | Clinical trials, phase 2 | Decreased HF symptoms, increased functional status, and reversal of negative LV remodeling | Human | Jessup et al, Circulation, 201158 |
| Stromal‐derived factor‐1 (SDF‐1) | Clinical trials, phase 1/2 | Safe and improved 6‐minute walk test, quality of life, and NYHA class | Human | Penn et al, Circ Res, 201359 |
| Adenylyl cyclase 6 (ADCY6) | Preclinical | Increased LV function, increased cAMP levels, reversal of dysfunctional β‐AR signaling, and increased survival Improved LV contractility |
Mice Pig |
Rebolledo et al, Hum Gene Ther, 200660 Roth et al, Circulation, 1999, 200261–62 Takahashi et al, Circulation, 200663 Lai et al, Circulation, 200064 |
| βARKct‐carboxy terminal peptide from GRK2 | Preclinical | Heart failure rescue Improved β‐AR signaling and contractile dysfunction |
Rabbit Human cardiomyocytes |
Shah et al, Circulation, 200165 Williams et al, Circulation, 200466 |
| S100A1 | Preclinical | Increased reuptake SR Ca2+, lowered Ca2+ leak, enhanced cardiac function, and reversed LV remodeling | Rat cardiomyocytes | Most et al, J Clin Invest, 200467 Pleger et al, Circulation, 200768 |
| Parvalbumin (PVALB) | Preclinical | Increased rate of Ca2+ removal and improved relaxation rate | Rat | Szatkowski et al, J Clin Invest, 200169 |
HF indicates heart failure; LV, left ventricle; NYHA, New York Heart Association; βARKct, β‐adrenergic receptor kinase; β‐AR, β‐adrenergic; SR, sarcoplasmic reticulum.