Use of Gene Therapy to Treat Dilated Cardiomyopathy

In this study, Dr. Sleeper will conduct a placebo-controlled, double blinded study to evaluate gene delivery approaches for treatment of Doberman Pinschers affected with DCM and CHF. If results show that the gene delivery slows progression of heart failure in Dobermans with DCM, the results will have significant ramifications for all dogs with heart disease, as calcium handling proteins are abnormally expressed in dogs with heart disease of varying causes.

The cardiology service at the University of Florida is looking to assess efficacy of therapeutic gene delivery using a virus vector.  The study is placebo controlled and double blinded; some dogs will receive the treatment and some will not. However, if there is a benefit to gene delivery, the placebo treated dogs will be treated with gene delivery once a benefit is recognized. To qualify for this study, the following criteria must be met:

Participation Requirements:

• Inclusion Criteria:
  • A diagnosis of DCM and previous evidence of congestive heart failure which has been controlled with medical management
  • A circulating neutralizing antibody titer to the virus vector of less than 1:20
  • Clear of extra-cardiac disease, congenital heart disease or primary mitral valvular disease
  • Owner agreement to authorize participation with informed consent and collection of the heart following euthanasia or death from any cause.

Owner's Responsibilities

At enrollment, an antibody titer, hematology and biochemistry panel will be used for screening purposes. Dogs will undergo a 3-minute electrocardiogram (ECG), a complete echocardiogram (ECHO) and the owners will complete a quality of life questionnaire. In order to participate in the study, dogs fulfilling the requirements will be randomly assigned to one of two groups: the placebo arm (cardiac injection with saline) or the gene therapy group (cardiac injection with the virus vector: AAV2/6-ARC-s100a1). Standard medical management for DCM and congestive heart failure will continue throughout the study in all dogs (pimobendan, angiotensin converting enzyme inhibitor and diuretic therapy). Saline instead of empty virus will be used as the placebo so that control dogs can undergo gene delivery if the treatment group demonstrates a significant improvement compared to the placebo group. Owners will need to commit to re-evaluations at 2, 4, 6, 9, and 12 months at the University of Florida following therapy.