This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lysosomal storage diseases are a heterogeneous group of disorders characterized by a genetic deficiency in one of several enzymes that are necessary for the breakdown of metabolites in many organs of the body. In some cases the enzyme deficiency has a profound affect on the central nervous system (CNS), leading to progressive neurodegeneration and premature death. Currently, several treatments are available to manage these diseases but no treatments exist that can delay or prevent neurodegeneration in the CNS. Therefore, the overall goal of this project is to exploit stem cells derived from bone marrow, referred to as mesenchymal stem cells (MSCs), as cellular vectors to reconstitute deficient enzyme activity in the brain as a means to delay and/or prevent neurodegeneration. Herein, MSCs are injected directly into the CNS of non-human primate (Rhesus macaques) infants and their overall engraftment levels and anatomic distribution in brain are quantified. These data are then correlated with effects on animal health, development, behavior, and motor skills to evaluate the safety of the overall approach. Additionally, since in most cases the MSCs are derived from an unrelated donor, the immune status of each transplant recipient will also be closely monitored to look for signs of rejection of the transplanted cells. Once the safety of the approach is established, the MSCs are transplanted into infant macaques afflicted with Krabbe disease, a form of storage disease that effects the nervous system, and their effect on disease progression is evaluated. By employing a relevant large animal model, data obtained from these studies will aide in developing more efficacious therapies for treating human infants afflicted with lysosomal storage disease that involved the CNS.
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