Diagnosis‎ > ‎

Work Done

AGU disorder is caused by the lack of lysosomal enzyme activity. Hence, several possible avenues exist that help deliver the needed AGA enzyme to body cells. Researchers investigated three different options, summarized below. 

Enzyme Replacement Therapy (ERT)
Aspartylglucosamine (AGA) enzyme can be manufactured in a laboratory to be injected via IV to an AGU patient on a regular basis. The circulating AGA enzyme is taken up by cells from the blood and corrects the disease in different organs such as the liver and kidneys. Ulla Dunder wrote a great thesis and published several articles showing that the correction can be achieved in the body, and possibly the brain using higher enzyme concentrations. This approach was tested in mice only. Unfortunately, no successful method to produce large quantities of the AGA enzyme for human use is currently developed.

Bone Marrow Transplant (BMT)
New bone marrow can generate normal blood cells on a permanent basis that produce AGA enzyme which can be passed into peripheral organs and possibly the brain. Successful experiments were done in mice, but results of BMT in AGU patientsworldwide are mixed. In most cases, patients after infancy did not show significant improvement in symptoms following BMT. Furthermore, side effects after BMT in some cases were problematic.

Gene Replacement Therapy (GRT)
In several studies various viruses were used to deliver a healthy gene to AGU mice either to a liver (by intravenous injection) or to a brain (by direct injection into the brain). In all cases, the transferred AGA gene successfully produced the enzyme, and the cells with the new gene were cleared from the toxic storage material. In addition, the targeted cells shared the AGA enzyme with their neighbors, creating a larger area of therapeutic effect. These studies were encouraging and showed that gene therapy could work.

One by one, most of the studies stopped because gene therapy/virus technologies at that time were very costly and/or were not developed enough. Lack of interest from big investors/donors due to small population of the affected individuals did not provide enough funding to continue the work. Unfortunately, it is a destiny for many rare diseases.