AKC Canine Health Foundation - 34

Gene Therapy for the Treatment of Doberman Dilated
Cardiomyopathy
Margaret Sleeper, VMD, DACVIM (Cardiology)
University of Florida
BIOGRAPHY
Meg Sleeper VMD graduated from the University of
Pennsylvania veterinary school cum laude and completed a
rotating internship in medicine and surgery at Mid-Atlantic
Equine Medical Center. After becoming board certified in
cardiology, she worked in the section of cardiology at Penn until
2015 when she became a clinical professor of cardiology at the
University of Florida veterinary school. She has published
numerous papers including over 80 peer-reviewed original
papers, over 50 review papers or case reports, and 4 textbooks. Primary research interests
include inherited heart diseases, in particular inherited cardiomyopathies, comparative
cardiology, and therapeutic gene transfer. She is on the editorial or review board of 11 journals
and has served on the research (2008-2011 and 2019 to the 2022) and examination (20052008)
committees for the American College of Veterinary Internal Medicine (Cardiology).
PRESENTATION ABSTRACT
Dilated cardiomyopathy (DCM) is a common disease in Doberman Pinschers, usually
terminating in sudden death or congestive heart failure (CHF) in spite of medical management.
According to one study in Dobermans, the 6-month survival from the first episode of CHF was
7.5% with 2 dogs surviving to 12 months.1 Gene delivery is a tantalizing approach that could
result in improved outcomes with various candidate transgenes. S100A1 is a Ca++ sensing
protein in the cardiomyocyte. Its functional properties are caused mainly by increased
SERCA2a activity, decreased diastolic SR Ca++ leakage and augmentation of the probability
the ryanodine receptor will be in an open state. Apoptosis repressor with caspase recruitment
domain (ARC) is a potent and multifunctional inhibitor of apoptosis, that can inhibit apoptosis
mediated by both the death receptor and mitochondrial signaling pathways.
Prior to gene delivery, dogs were assessed for presence of vector directed neutralizing
antibodies and were enrolled if the titer was <1:20. Gene delivery into the myocardium (n=1) or
coronary arteries (n=10) was performed to cause overexpression of myocardial s100A1 and
ARC (the two genes were piggybacked in one virus) in Doberman Pinschers that had been
diagnosed with DCM and compensated CHF. Dogs were assessed immediately prior to
treatment and after treatment at 2, 4, 6, 9 and 12 months (or until death) with complete clinical
laboratory testing, electrocardiography, echocardiography and quality of life questionnaire
(FETCH).
For the coronary approach, delivery was considered fair in 1 dog, good in 3 dogs and excellent
in 6 dogs. Dogs survived 1 to 16.5 months from the initial diagnosis of congestive heart failure
with a mean survival of 6.9 months. For dogs with excellent viral delivery, mean survival was 9
months if the dog that succumbed to a fatal arrhythmia was removed.
1 Calvert C et al. JAVMA 1997.
2023 National Parent Club Canine Health Conference
Presented by the AKC Canine Health Foundation and Nestlé Purina PetCare

AKC Canine Health Foundation

Table of Contents for the Digital Edition of AKC Canine Health Foundation