Method of gene transfer for the treatment of recessive catecholaminergic polymorphic ventricular tachycardia (CPVT)
The present invention concerns a method for the treatment of recessive Catecholaminergic Polymorphic Ventricular Tachycardia comprising delivering a gene into a cardiac cell.
1. A method of treating recessive catecholaminergic polymorphic ventricular tachycardia (CPVT) in a human patient that exhibits arrhythmia and has a deleterious mutation in the gene encoding calsequestrin 2 (CASQ2) protein, wherein said method comprises introducing an adeno-associated viral (AAV) vector comprising a nucleic acid encoding a wild-type CASQ2 protein into a cardiomyocyte in said patient, wherein the amino acid sequence of said CASQ2 protein is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, wherein administration of said AAV vector to said patient results in an antiarrhythmic effect on said patient, thereby treating CPVT in the patient.
2. The method of claim 1 , wherein said AAV vector is an AAV2/9 vector.
3. The method of claim 1 , wherein the amino acid sequence of said CASQ2 protein is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.
4. The method of claim 1 , wherein said mutation is a homozygous mutation.
5. The method of claim 4 , wherein said homozygous mutation is R33Q.
6. The method of claim 1 , wherein physiological levels of expression of CASQ2 are restored following administration of said AAV vector to said patient.
7. The method of claim 1 , wherein physiological abundance and spatial organization of triadin and junctin are restored following administration of said AAV vector to said patient.
8. The method of claim 1 , wherein intracellular Ca 2+ storage and Ca 2+ fluxes are restored following administration of said AAV vector to said patient.
9. The method of claim 1 , wherein said anti-arrhythmic effect is assessed by electrocardiography.