DPCA National Features Advances in Research of Genetic & Cardiac Diseases

Among the most concerning health conditions to breeders and owners of Doberman Pinschers are genetic conditions, such as wobbler syndrome, and the complex heart disease, dilated cardiomyopathy (DCM). Organizers of the Health Night Seminar, held Oct. 4 at the 87th annual Dober­man Pinscher Club of America (DPCA) National Specialty in Fort Mitchell, Ky., invited prominent veterinary researchers to discuss their advances in better understanding these diseases plus others that affect Dobermans.

Mark Neff, Ph.D., the founding director of the Program for Canine Health and Performance at the Van Andel Research Institute in Grand Rapids, Mich., and Luis Braz-Ruivo, D.V.M., D.V.Sc., DACVIM (Cardiology), of the Dogs & Cats Veterinary Referral in Bowie, Md., were the featured presenters at the Health Night Seminar. Additionally, a team of board-certified veterinary cardiologists provided a no-cost comprehensive cardiac screening clinic to identify Dobermans in the early asymptomatic or occult stage of DCM.

"We were delighted to bring in such distinguished veterinary experts to speak at the Health Night Seminar," says Kathy Davieds, D.V.M., chair of the DPCA National Specialty Health Seminars Committee. "The opportunity to provide the cardiac screenings at no cost and to have these esteemed veterinary cardiologists examine our Dobermans was a bonus. This is the first time we've offered such comprehensive screenings at no cost to owners."

Tapping into a Doberman Database

With a rich database of blood samples and pedigree information about Doberman Pinschers, the Van Andel Research Institute has made progress in learning about wobbler syndrome and other disorders that affect Dobermans.

"We have far more data on the Doberman breed than any other breed," Neff says. "The more data we have, the more power we have to understand the ramifications of the diseases and conditions affecting Dobermans, and for that matter, to learn how these findings may translate to other breeds and potentially humans."

Neff is seeking a genetic link to cervical spondylomyelopathy (CSM), commonly called wobbler syndrome. A disease that can lead to partial or complete paralysis, wobbler syndrome takes its name from the wobbly gait of affected dogs.

Doberman Pinschers are predisposed to slippage of the intervertebral disks in the narrow veterbral canal surrounding the spinal cord. The condition causes pressure on the spinal cord and nerve roots, resulting in mild to severe instable walking that worsens over time. Dogs suffering from wobbler syndrome may have neck pain, general weakness and difficulty getting up from a lying position.

Chronic active hepatitis (CAH) also is being studied. "We believe this disease in Doberman Pinschers may involve the accumulation of copper in the liver," Neff explains.

Ongoing inflammation that results in progressive damage to the liver cells, CAH causes scar tissue that overtakes healthy liver issue and eventually leads to liver failure and death. Early signs, which include poor appetite, intermittent vomiting and lethargy, occur in other health conditions, so owners often do not learn their dog has CAH until the disease progresses to a severe condition. Dogs with advanced disease may suffer from fluid buildup in the abdomen, or liver encephalopathy, which is the inability of the liver to eliminate ammonia and other toxins, and ulcers in the gastrointestinal tract.

Though it is not known definitely whether CAH is an inherited disease, the higher incidence of this disease in Doberman Pinschers relative to other breeds suggests the involvement of genetic factors. These factors may interact with environmental influences.

"A benefit of identifying causal genes is that it increases the power for detecting nongenetic influences," Neff says. He hopes that while this disease in Dobermans is distinct from one in Standard Poodles, the genes involved may function in a common biochemical pathway. If so, progress in one project may benefit the other.

Neff's enthusiasm for working with the Doberman Pinscher community stems from their first success. Two years ago, Neff's laboratory at Van Andel began research that recently culminated in the discovery of a single-gene mutation responsible for an autosomal recessive disorder that causes bilateral congenital vestibular disease with juvenile deafness, referred to by breeders as "dings." In affected dogs, the vestibule, a cavity in the inner ear containing tiny bones and sensory cells, begins to deteriorate shortly after birth. Signs of the disorder include head tilting, lack of coordination and circling. Deafness occurs around 3 weeks of age.

"Discovery of the gene was a direct consequence of working with breeders who were enthusiastic about finding a gene," Neff says. "This is true of all successful studies in canine genetics. By partnering with the breed community, great progress can be made."

Other diseases that affect Dober­mans that are being studied at Van Andel include: head bobbing syndrome, canine compulsive disorder and two cancers, osteosarcoma and melanoma. The wide range of genetic and health disorder research under way at Van Andel is possible because of the support the institute has received from Doberman Pinscher enthusiasts. As an example, a recent anonymous online health survey available for two weeks on the DPCA website (www.dpca.org) received 1,700 responses. Respondents could provide contact information if they were interested in submitting blood samples for further research. More than 1,400 people provided their contact information.

"The best dog biologists are not people in laboratories like me, but rather, the breeders and owners who have built up decades of insights through their experiences," Neff says. "That is why their participation in studies such as these is so critical. Developing genetic tests that can be used by breeders to guide their breeding decisions is the end game of our research."

Study Changes DCM Treatment Protocol

Dilated cardiomyopathy is an inherited, irreversible heart muscle disorder that affects 25 to 50 percent of Doberman Pinschers. It causes the heart muscle to become weak, leading to heart failure and ventricular arrhythmia, or abnormal, erratic heartbeats that fire too closely together. This can cause a dog to become weak or faint. Some dogs recover after fainting, yet others die suddenly.

About 50 percent of Dobermans with DCM die suddenly due to ventricular arrhythmias. In 33 percent of Doberman with DCM, sudden death is the first clue they had the disease. Ventricular arrhythmias and sudden death due to DCM can occur in Dobermans as young as 3 to 4 years of age.

Dobermans with DCM that do not die suddenly generally appear normal until they are 4 to 7 years old, when their heart muscle is no longer able to compensate for the disease and becomes significantly weakened and dilated. As the disease progresses, congestive heart failure occurs when the heart can no longer adequately pump blood to the body.

As the heart dilates to compensate for the weakened heart muscle, it holds a greater volume while the thinned walls continue to weaken. Fluid typically backs up into the dog's lungs causing pulmonary edema, but it also can back up into the abdomen causing ascites. During this symptomatic stage of the disease, owners often notice signs of heart failure, such as shortness of breath, rapid breathing, coughing, weakness, and lethargy. Symptomatic DCM usually is diagnosed in Dobermans around 7 ½ years of age, after many have already been bred.

Drug therapy offers palliative care for symptomatic DCM but does not cure the disease. Medications that strengthen the heart muscle make it easier for blood to flow forward and help remove the extra fluid accumulation in the lungs or abdomen. While medications can help dogs feel better and prolong life, the disease still is terminal. Dogs with congestive heart failure typically live less than a year.

Dilated cardiomyopathy generally is present for six to 18 months before a dog develops heart failure. The early stage of the disease, known as the asymptomatic or occult stage, is difficult to diagnose because affected dogs are apparently healthy, feel well and often have no outward signs of the disease even when evaluated by a veterinarian. Tests such as echocardiography, an ultrasound of the heart, and Holter monitoring, a 24-hour electrocardiogram (EKG), are required to definitively diagnose the disease during the asymptomatic stage.

A recent clinical study, called The PROTECT Study, showed that Dobermans with asymptomatic DCM that received pimobendan, which is marketed as Vetmedin® by Boehringer Ingelheim Vetmedica, remained asymptomatic 63 percent, or nine months, longer than Dobermans that received a sugar pill placebo. About 1,000 apparently healthy Dobermans in the U.S., U.K. and Canada were screened to recruit the 76 dogs that took part in the five and a half year study.

In the study, the average time for Dobermans with asymptomatic DCM, characterized by a weak heart muscle documented with echocardiography, that received Vetmedin to develop heart failure or die suddenly was 24 months, compared to 15 months for the dogs in the placebo group. Historically, only one other class of medication, ACE (angiotensin-converting-enzyme) inhibitors, such as enalapril or benazepril, has been used to treat dogs in the asymptomatic stage.

As a result of the PROTECT study, cardiologists now are recommending Vetmedin with or without an ACE inhibitor and anti-arrhythmic medications, if appropriate, for Dobermans with asymptomatic DCM based on an echocardiogram. Vetmedin currently has not been proved effective in Dobermans with asymptomatic DCM characterized only by arrhythmias; thus, Vetmedin should not be used in dogs with normal echocardiograms.

Since the study showed a benefit to starting Vetmedin in Dobermans in the asymptomatic stage of DCM, the ability to identify those dogs has become increasingly important. The best screening tests, which also are the most definitive diagnostic tests, are an echocardiogram combined with a Holter monitor test. Since these tests are not available at all veterinary clinics, many Dobermans are not screened as often as they should be.

The DPCA recommends that Dober­man Pinschers have a baseline echocardiogram and Holter monitor test when they are 1 to 2 years of age and that dogs being used in breeding programs should be tested every six months thereafter. This requires a significant financial commitment for owners and breeders over the lifetime of a dog.

The use of blood tests, called cardiac biomarker tests, to identify apparently healthy Doberman Pinschers that have a high risk of developing asymptomatic DCM and that would benefit from definitive testing was the focus of the veterinary cardiology specialists who performed the cardiac evaluations at the screening clinic held during the DPCA National. A promising cardiac biomarker in Doberman Pinschers is NT-proBNP, which the heart muscle releases in increasing amounts as it develops DCM. Preliminary studies of this biomarker will be published in the Journal of Veterinary Internal Medicine.

Sonya G. Gordon, D.V.M., D.V.Sc., DACVIM (Cardiology), associate professor of cardiology at Texas A&M University College of Veterinary Medi­cine and Biomedical Sciences in College Station, one of the investigators, says, "We are trying to find cost-effective ways for Doberman owners and breeders to screen annually for this disease. NT-proBNP will not replace an echocardiogram or Holter monitor test, as they are required to diagnose DCM, but screening could become more cost-effective if we have a blood test to identify Dobermans that would benefit most from these definitive tests.

"Early diagnosis can lead to early treatment with Vetmedin, which we now know will prolong the asymptomatic stage and life of the dog. In addition, an owner who knows his or her dog is predisposed to heart failure may be better able to identify subtle signs of a worsening condition in that individual dog."

Purina appreciates the support of the Doberman Pinscher Club of America and particularly Judith Brown, chair of the DPCA Health Research Evaluation Com­mittee, in helping to identify topics for the Purina Pro Club Doberman Pinscher Update newsletter.

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