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A line of golden retriever dogs (GRMD) exhibits clinical and pathological signs of muscular dystrophy similar to those seen in boys with Duchenne muscular dystrophy (DMD). The results of stem cell transfer experiments in these dogs were released as an advance online publication in the journal Nature on November 15, 2006. This study by a group of Italian researchers showed that it is possible to transplant stem cells into the dogs and that some of the muscles did produce dystrophin. There were differences between dogs in the results, but the walking ability was preserved in several of the dogs. Generally, these GRMD dogs lose this ability and die by the age of one year.
Stem cells (mesoangioblasts) used were isolated from the walls of small blood vessels. These cells work well for several reasons: they are easy to isolate; they grow quickly; and they can pass through blood vessels to get into the muscles. Treatment was by injection of the cells into an artery of the GRMD.
Thirteen GRMD dogs were divided into 3 groups:
The results were generally better for the 6 dogs treated with donor stem cells from healthy dogs (heterologous) and treated with immune suppressant drugs (cyclosporine or rapamycin). There was variation in the response of these dogs, but two of them were walking fairly well after the treatment was halted and one other was better than the control dogs. The muscles of these GRMD showed variability, but, overall, there was improvement in the microscopic appearance of the muscles of the treated dogs. There was evidence of dystrophin production in many muscle fibers. Dystrophin is lacking in the muscles of the GRMD dogs as it is in patients with Duchenne muscular dystrophy.
The GRMD dogs that were treated with their own stem cells, modified with the gene for micro-dystrophin, did not fare as well as those treated with the heterologous cells. Although there was some evidence of improvement in the microscopic appearance of some muscles, these dogs did not have improved mobility. This may have been because the micro-dystrophin was not effective. Results may be better if the gene for a larger, more functional dystrophin is used. Another possibility is that the micro-dystrophin used in this study was derived from human dystrophin, rather than dog dystrophin. Dog dystrophin may prove to be more effective.
These results are encouraging for the treatment of DMD. The evidence from this study warrants follow-up. There must be further refinement in animals before moving the study into human trials. This will take several years. However, the possibility of testing in human subjects is on the horizon.
The study was conducted by Maurilio Sampaolesi, Guilio Cossu and others of the San Raffeale Scientific Institute in Milan , Italy .
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