Long-term follow-up of gene therapy for dog heart disease

Abstract

In large breed dogs, dilated cardiomyopathy (DCM) is the main cause of congestive heart failure (CHF) and sudden cardiac death. The underlying etiology of DCM is usually not definitively identified; however, in predisposed breeds a hereditary etiology is often suspected. Other etiologies, such as toxins and infections, have also been documented or suspected to cause DCM in dogs. Conventional drug treatment cannot reverse disease progression but can only control the signs of heart failure as they occur. Cytoprotective gene therapy with Vascular Endothelial Growth Factor-B167 (VEGF-B167) has been shown to be an effective alternative therapy that can halt disease progression in preclinical experimental studies in dogs. This study reports the long-term clinical and echocardiographic follow-up of a 6-year-old St. Bernard dog with DCM treated with intracoronary administration of VEGF-B167 gene delivered by adeno-associated viral vectors (AAV- VEGF-B167). Monitoring was performed at 1, 3, 6, 9, 12, 18, 24 and 36 months post-procedure (T0-T8) including clinical, laboratory and instrumental examinations. The dog reached T8 in good clinical condition. Comparing echocardiographic parameters from T0 to T8, ejection fraction (EF%) did not worsen, indeed showing potential improvement (30% to 38% from T0 to T8 respectively) (Simpson method). Other parameters of disease progression varied minimally over the course of the study. From T0 to T8, no relevant change in medical therapy was necessary. The dog survived 341 days from the last follow-up and died of sudden death 1436 days after the procedure (T0). A survival time of 4 years in good health is an excellent outcome suggesting a possible protective role of VEFG-B167 in slowing disease progression in this dog.