Mucopolysaccharidosis I, one disease of a group of inherited lysosomal enzyme deficiencies, is recognized in man, cats, and now in dogs. In no instance is effective treatment well documented.
The aim of this project is to utilize a newly discovered canine model of MPS I to evaluate the benefit of a currently controversial treatment procedure, namely bone marrow transplantation. This is the first opportunity to evaluate this procedure using an animal model of the human disease. Continued development of the animal model, which now exists only at this institution, is also a major goal of the project. Dogs which are homozygous for Alpha-L-iduronidase deficiency (MPS I) will be subjected to marrow transplantation from heterozygous littermates and homozygous, normal littermates. In each case, DLA histocompatibility and mixed leukocyte culture pairing or donor-recipient pairs will be performed. A total of 12 dogs will be transplanted during the 3 year project. An equal number of control, affected littermate dogs will be maintained and studied as a basis for evaluation of the benefit of bone marrow transplantation. Pre- and post-transplantation studies will include, but not be limited to, evaluation of differences in clinical disease progression, urinary glycosaminoglycan profiles, tissue enzyme levels, and ultrastructural lesions. Effects of transplantation prior to and after the development of clinical signs will be compared to see if clinical disease can be prevented, as well as slowed, by this procedure. All experimental and breeding animals will be maintained under conditions which meet all N.I.H. guidelines and they will be given vigorous health care. It is hoped that the value of this new animal model will be realized when effective, safe treatment of mucopolysaccharidosis, and perhaps other lysosomal storage diseases, is available. As bone marrow transplantation seems to offer some important advantages towards this goal, and since this procedure is well developed in dogs, this project represents both a logical and important starting point for the use of this new animal model of human disease. Accomplishment of the goals to this proposal will provide the basis for future studies involving new therapeutic regimes such as genetic modification of affected animals.
