Here is some interesting information passed on to my by Cinnias breeder. REPAIRING FAILING HEARTS: TREATING DILATED CARDIOMYOPATHY WITH STEM CELL PRODUCTS RICHARD VULLIET,PHD,DVM U.C. DAVIS REGENA-VET LABORATORIES DAVIS, CALIFORNIA In previous pilot studies, this investigative team demonstrated that donor bone marrow stem cells (MSCs) appeared to arrest progression, and possibly reverse, dilated cardiomyopathy (DCM) in Doberman Pinschers. They found that MSCs administered systemically will migrate to diseased myocardium. Most of the treated dogs showed improvement in activity, attitude and/or cardiac parameters. Without the use of any other medications, their longest lived dog survived for 450 days from the onset of signs of CHF. However, the duration of the beneficial effects appear to be limited, presumably due to immunological responses to the donor cells. The limited duration, costs of repeated patient evaluation, and multiple stem cell administrations make stem cell therapy beyond the reach for most Dobe owners. Affordability is the key for implementation of effective stem cell therapy of dogs with DCM. Aware of this reality, this team will now utilize the paracrine properties (secretion of growth factors) of MSCs and test if their secreted growth factors are effective in treating DCM-affected patients. If successful, this approach will make the treatments safer, easier to administer and more affordable. In three pilot dogs treated with these growth factors (the preparation is referred to as Regenavate), all had notable improvement in exercise tolerance and slight improvement in cardiac parameters. This groups working hypothesis is that growth factors produced by the MSC will treat DCM without the immunological complications. They believe that Regenavate will arrest the loss of cardiomyocytes, stabilize failing cardiomyocytes, improve cardiac function and ultimately, patient survival, as has been shown with MSCs in laboratory animals. Using a modified phase I/phase II FDA procedure, Regenavate will be tested in Dobes with DCM. Initially, DPs with more advanced DCM will be treated primarily to verify safety. Following confirmation of safety, Regenavate will be tested in a larger trial using less severely affected DPs (which should have less scar tissue and fibrosis in their hearts and improved potential to respond). The results from each dog will be compared with their pretreatment values. In phase II, the number of animals treated will be increased to establish statistically significance. Based on the results from the pilot dogs, they expect that Regenavate-treated DCM-dogs will have improved cardiac values and increased survival. Regenavate treatment also allows the simultaneous use of conventional veterinary medical treatments. More important, once proven, this technology should be affordable for the average Dobe owner and can be rapidly disseminated to local veterinarians. This study will be supervised by Richard Vulliet, Ph.D, DVM and Dr Pamela Rosman through ReGena-Vet Laboratories, LLC in Davis, CA. ReGena-Vet Laboratories has developed procedures for shipping cells within the US so that patients can be treated by their local veterinarians and/or veterinary cardiologists. If you are interested in having your Dobe participate in these clinical trials, please contact ReGena-Vet Laboratories at regenavetlabs@gmail for further information. -------------------------------------------------------------------------------- Project Title: The role of the PDK4 mutation in Doberman Pinschers with Dilated Cardiomyopathy and Potential Therapeutic Options Principal Investigator(s): Amara H. Estrada, DVM, DACVIM Associate Professor and Associate Chair Small Animal Clinical Sciences University of Florida College of Veterinary Medicine PO Box 100126 Gainesville, Florida 32610-0126 [email protected] 352-294-4438 Doberman Pinschers account for at least 50% of all cases of canine DCM, a cardiomyopathy where the cardiac muscle does not pump blood efficiently. Once begun, the pathology of this disease progresses quickly and is eventually fatal. A deletion of the PDK4 gene has been identified in 75% of Doberman Pinschers with DCM. The PDK4 gene allows for production of a mitochondrial protein involved in cellular metabolism. Mitochondria are organelles inside cells that provide energy for the cells. The possession of the mutation and its effect on mitochondrial function has not yet been established, and this is required in order to consider gene replacement as a possible therapeutic option. It is believed that fatty acid oxidation, a pathway in which the PDK4 enzyme plays an important role, is impaired in Dobermans with this condition. Cardiac cells produce energy mainly from fatty acids. It is believed that the mutation in this disease, leads to a reduction in PDK4 activity in cardiac cells, thus making them more reliant on less effective energy production pathways. This shift in metabolic process within cardiac cells would thus affect contractile function. If the PDK4 mutation were present in a patient, it would be deficient in all types of cells, not solely cardiac cells. The ability of these cells to produce energy can be measured by oxygen consumption rate (OCR), as a measure of metabolic efficiency. This study will use fibroblasts, derived from cells following small skin biopsies to measure OCR. Using fibroblasts will allow our team to investigate this genetic mutation without necessitating more invasive studies such as cardiac biopsy, in order to understand the metabolic changes which occur with this mutation. The purpose of this study is (1) to compare OCR of skin fibroblasts from Doberman Pinschers with DCM and the PDK4 mutation, and normal Dobermans; (2) to evaluate in vitro (bench top) whether treatment of skin fibroblast from Doberman Pinschers with DCM and the PDK4 mutation improves metabolic efficiency (OCR) and finally (3) evaluate effect of gene replacement therapy on cardiac function and survival in Doberman Pinschers with DCM and the PDK4 mutation.
Posted on: Sat, 29 Mar 2014 00:44:44 +0000
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