On January 27, 2010, Dr. Amara Estrada performed the first stem cell transplant on a DCM affected male Doberman. Dr. Estrada’s study is supported by the DPCA in the total amount of $77,500.00 ($65,000 was donated from the DPCA Health fund, and an additional $12,500 is the result of earmarked personal member donations). This is a very exciting and promising procedure, and DPCA will be informed of the results when available. Contact Amara Estrada, DVM at the University of Florida if you have a dog that may be eligible for inclusion in this study. Dr. Estrada can be reached at EstradaA@vetmed.ufl.edu. Continued substantial support of projects that target DCM and other Doberman specific problems is the goal of this committee.

On another front, a test has been developed for Juvenile Renal Disease in Dobermans. This is the least understood kidney disorder in dogs, yet is likely the most frequent and once diagnosed is fatal. For further information regarding this new test, contact Mary H. Whiteley, PhD at DOGenes, Inc.

www.dogenes.com.

Remember that DPCA is a 501c3 organization and donations to health projects are always tax deductible. Contact me for further information. 

Judith A. Brown

Chairman, Health Research Evaluation Committee

judithabrown@sbcglobal.net

1. Institution: University of Florida

2. Date of report: 3/5/2010

3. Title of project: Cardiac Cellular Transplantation for Dilated Cardiomyopathy in Doberman Pinschers

4. Names of investigators:

Principal Investigator: Amara Estrada, DVM, ACVIM Assistant Professor estradaa@vetmed.ufl.edu

Co-Investigators:

Thomas Conlon, PhD, Assistant Professor of Pediatrics, Director, Powell Gene Therapy Toxicology Ctr. Gainesville, FL 32610, Email: conlon@peds.ufl.edu

Brandon Pogue, DVM, Resident in Cardiology, Small Animal Clinical Sciences, University of Florida, College of Veterinary Medicine, 

Gainesville, FL 32610-0126, Fax: 352-392-6125, Email: pogueb@vetmed.ufl.edu

5. Start date: 1/1/2010

6. End date: 1/1/2012

7. Summary of progress to date as related to each of the original objectives:

Specific Aim #1: To implant tmAAV SDF1 transduced MSCs via retrograde coronary venous infusion into the myocardium of Doberman Pinschers affected with DCM. Stem cells were obtained from a commercial source and have been successfully cultured, amplified and maintained within the Powell Gene Therapy Center at the University of Florida Toxicology Core to produce an adequate number for implantation. These cells are now currently under investigation for their ex vivo ability to differentiate into myocardial cells. Cells were transduced with tmAAV2 SDF-1, to enhance cell retention, and delivered by retrograde infusion into the coronary venous system of two Doberman Pinschers with Dilated Cardiomyopathy. We have another four dogs scheduled in the next month for delivery of cells as well.

Specific Aim #2: Determine acute effects of cellular transplantation of tmAAV SDF1 transduced MSCs into the myocardium of Doberman Pinschers affected with DCM. Both of the clinical patients who underwent the injection of cultured/transduced MSCs did very well. We saw transient arrhythmias which occurred acutely, rapidly dissipated and were well tolerated clinically without adverse sequela.

Specific Aim #3: Determine chronic effects of cellular transplantation of tmAAV SDF1 transduced MSCs into the myocardium of Doberman Pinschers affected with DCM. We have not had any long term follow up on these two patients at this point in time.

8. Describe any changes in scientific goals as outlined in original proposal.

We have decided to include patients who have clinical signs in the study as we had numerous requests from distraught owners. Our initial concern for inclusion of patients in heart failure was regarding the patient’s ability to tolerate anesthesia. After consultation with Judy Brown,

we decided to enroll a patient in heart failure. This patient was in biventricular heart failure and he did very well during the procedure so we now feel less nervous about this aspect. We have also submitted a preproposal to the AKC/CHF for this project using the preliminary data gathered from these first two patients. If accepted for a full proposal and then eventually funded, we would use the AKC/CHF grant for the occult group of dogs and the Doberman Pinscher Club of America grant for dogs with heart failure so that we are able to offer this treatment modality to all Dobermans affected with DCM.

Schedule of unfinished experiments; completion date: We have 4 more Dobermans scheduled for stem cell transplantation next month.

9. List planned and accepted publications. Abstracts are attached at the end of this report.

Planned and accepted publications pertaining to project:

Planned manuscripts

Estrada AH, et al.

Safety and Efficacy of Stem Cell Transplantation in Doberman Pinschers with Dilated Cardiomyopathy.

Invited international presentations

Estrada AH. Stem Cell Therapy for Heart Disease, North American Veterinary Conference, Orlando, Florida, 2010. Estrada AH. Stem Cell Therapy for Heart Disease, American College of Veterinary Internal Medicine Cardiology Specialist Proceedings: Montreal, Canada 2009.

Planned abstracts

Estrada, et al. Safety and Efficacy of Stem Cell Transplantation in Doberman Pinschers with Dilated Cardiomyopathy.

Plan to submit abstract to either ACVIM or ESVIM 2011.

10. If live animals are involved in this study, including client owned animals, please comment briefly on the animal care protocols being used (pain management, enrichment, etc.).

This study has been approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Florida and the Clinical Research Review Committee. The assigned IACUC protocol number is E937. The study does not induce disease as it is clinical research using owned animals which already have the disease process which will be studied. There is minimal distress caused by the surgery for transplantation of cells. The study utilizes the complete facilities of the University of Florida Veterinary Medical Center to insure that the patients in the study receive more than adequate care. Throughout the study patients are in care of their owners following stem cell transplantation and release from the hospital.

11. Lay-language description in 100 words or less of your progress to date.

Treatment for dilated cardiomyopathy (DCM) is frustrating and a great need exists for better treatment options. Recently in human medicine, injection of adult stem cells into failing heart muscle has been employed with success causing improvement in heart function and survival. This study aims to use stem cell therapy for Doberman Pinschers affected with DCM, in hopes of improving cardiac function and providing a new treatment option for this devastating disease.

KIDNEY DISEASE TEST FOR RENAL DYSPLASIA IN DOBERMAN PINSCHERS

January 30, 2010

I am writing to you to let the Doberman community be aware of a test that we have developed for kidney disease (renal dysplasia) in your breed. We have confirmed that the mutation that we discovered originally in Lhasa apsos, Shih tzus and Miniature schnauzers as well as many other breeds correlates with a clinical case of renal dysplasia in your breed.

This disease is probably the least understood kidney disorder in dogs, yet is likely the most frequent. The reasons that this disease is overlooked at many fold: there are a wide range of clinical manifestations, the diagnosis is only by wedge biopsy, which is seldom done, and the age onset can range from young puppies to at least 10 years of age. Unfortunately, these adult cases are rarely reported back to the breeder, and veterinarians are unlikely to consider that this this inherited but is congenital as there are usually not any affected relatives. The cases in puppies are usually the ones that are given the most attention, however they are the the less frequent than the adult cases. The mode of inheritance is dominant with incomplete penetrance, meaning that all animals that have one or two copies of the mutation may or may not have the disease. The penetrance is low, however once a diagnosis is made, the disease is fatal.

For the month of February we will be offering this test for $75.00 because we believe that it is important that the Doberman breed is aware of the frequency of this mutation so that they can move forward to eliminate this disease. This will be available on our website www.dogenes.com as a special. I hope that the Doberman breeders will take advantage of this offer so that they can improve the overall health of the breed.

The scientific reference for RD in Dobermans is listed below.

Thank you for your help in this matter,

J Am Vet Med Assoc. 1983 Mar 1;182(5):481-5.

Juvenile renal disease in Doberman Pinscher dogs.

Chew DJ, DiBartola SP, Boyce JT, Hayes HM Jr, Brace JJ.

Renal failure was diagnosed in 22 young Doberman Pinscher dogs. The clinical findings were anorexia, weight loss, vomiting, lethargy, polydipsia, polyuria, and dehydration. Laboratory findings were azotemia, hyperphosphatemia, lymphopenia, nonregenerative anemia, hypercholesterolemia, and proteinuria. The kidneys were characterized pathologically by glomerular sclerosis, cystic glomerular atrophy, tubular dilatation, tubular atrophy, mononuclear interstitial inflammation, interstitial fibrosis, interstitial mineralization, and hyperplasia of the collecting duct epithelium. 

Sincerely,

Mary H. Whiteley, Ph.D

DOGenes Inc.

www.dogenes.com