Because enzyme replacement therapy is so effective for patients with Type 1 (non-neuronpathic) Gaucher's disease, we have performed investigations to try to deliver the required glucocerebrosidase to neurons in the central nervous system in order to treat patients with the neuronpathic forms of this disorder. We found that mannose-terminal glucocerebrosidase is stable within the substance of the brain following convection-enhanced intracerebral injection. Moreover, the enzyme migrates from the site of injection toward the cortex where neurons containing stored glucocerebroside occur. We have discovered that mannose-terminal glucocerebrosidase is taken up by cultured LAN-2 and other differentiated neurons in tissue culture, but this uptake is different from that mediated by the mannose lectin on the plasma cell membrane of macrophages. We shall determine the nature of the receptor on neurons and attempt to exploit it to deliver glucocerebrosidase and other supplemental enzymes to treat various neurometabolic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002845-06
Application #
6163060
Study Section
Special Emphasis Panel (DMNB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code