Lysosomal Diseases Research Unit, Chemical Pathology

Alpha-mannosidosis is an inherited lysosomal storage disease (LSD) causing progressive mental retardation in affected patients. Patients presenting with this disease have a life expectancy anywhere between 3 years and adulthood, but suffer from a worsening mental condition throughout their life. Although bone marrow transplantation has shown limited success as a treatment for this disease, it is not suitable for all patients and is a high risk procedure.
Stem cells are cells in the body defined as having the potential to change into multiple other cell types under appropriate conditions. Neural stem cell therapy involves the injection of stem cells into the patient's brain, such that they can integrate with other cells to provide a therapeutic effect. This strategy is particularly promising for the treatment of LSDs, because many of these disorders, including alpha-mannosidosis, are caused by the deficiency of a single protein. The alpha-mannosidosis guinea pig represents an excellent animal model to study brain pathology, due to the similarity of disease symptoms and progression to that observed in humans.
Our preliminary studies have shown that neural cells derived from mouse embryonic stem cells can survive in the guinea pig brain for at least two months. Vectors to genetically modify these cells to manufacture large amounts of alpha-mannosidase (deficient in alpha-mannosidosis) are currently under construction. Results of previous cell therapy studies by other groups suggest that implantation of stem cells expressing large amounts of therapeutic protein in the brain of affected animals should provide significant and measurable clinical benefit.