Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disease caused by the deficiency of sulfamidase. MPS IIIA is characterized by progressive neurodegeneration accompanied by loss of social skills and aggressive behavior, hyperactivity and sleep disturbance. Somatic features are often mild and variable. To correct the brain pathology in lysosomal storage diseases, our group and others have successfully introduced genes encoding the missing enzymes into brain. The basis of this gene therapy method lies in the efficient
secretion of lysosomal enzymes. If the enzyme was effectively secreted from gene corrected cells, then it could be uptaken by the nearby cells, and broad correction in the brain could be achieved. In our unpublished work, we find that the how well lysosomal enzymes are secreted vary greatly. In this work, we propose to use genetic methods to modify sulfamidase to improve secretion and temper degradation to provide for greater therapeutic benefit.
– Beverly Davidson, PhD
The Children’s Hospital of Philadelphia