00900-A: Immunological Treatment of Canine Dilated Cardiomyopathy Using a T-Lymphocyte Modulator
Grant Status: Closed
Project SummaryLarge breed dogs are predisposed to developing dilated cardiomyopathy (DCM), a disease that causes the heart to enlarge and not function properly, leading to heart failure and death. Current drug treatments improve the function of the heart and control the signs of congestive heart failure but do not address the underlying cause. Although the precise cause of DCM is unknown, it is now accepted that certain forms of DCM are accompanied by a change in T-lymphocyte activity, which may exacerbate the condition by immune dysregulation. T lymphocytes, appear to have a regulatory effect on cardiac remodeling, thus bridging the gap between the immune system and cardiac function. Recently "therapeutic vaccines" targeting the T-lymphocyte Receptor (TCR) have been developed and shown to restore normal T lymphocyte balance, which restores heart function in various laboratory models of DCM. The purpose of this study was to determine whether immunization with a TCR therapeutic vaccine in dogs with DCM improves clinical outcome and cardiac function. In this study 2 Great Danes and 2 Doberman Pinschers with well established DCM, which were stabilized on current medication and under the care of veterinary cardiologists, were immunized with a TCR vaccine and evaluated clinically and by electrocardiography for up to 90 days. Three of the 4 dogs survived the experimental period and beyond and did well clinically. One Doberman Pinscher died of unreported causes after the Day 60 examination. Because the dogs were clinically stabilized at the time of enrollment, average clinical signs did not appreciably change. However, patient specific changes were noted by either the veterinarian or the owner in all dogs at some point after TCR vaccination, providing valuable insight into patient specific clinical improvements. Analysis of the electrocardiographic data revealed definite improvement in key measurements which are consistent with improved cardiac function. These included improvements in stroke volume index (SVI), left ventricular fractional shortening (LVFS) and ejection fraction (LVEF). The improvements in LVFS and LVEF were statistically significant, despite the small number of dogs in the study. The results of this pilot study strongly suggest that TCR vaccination improves cardiac function in dogs with DCM, apparently by immunologic mechanisms that promote cardiac muscle remodeling. If confirmed, the TCR vaccine would represent a new biologic approach for cardiovascular medicine. These findings encourage expanded clinical trials in dogs with DCM at various stages of the disease.
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