Iminosugar-Based Inhibitors Improve Survival in Sandhoff Disease Mice
Author Information
Author(s): Ashe Karen M., Bangari Dinesh, Li Lingyun, Cabrera-Salazar Mario A., Bercury Scott D., Nietupski Jennifer B., Cooper Christopher G. F., Aerts Johannes M. F. G., Lee Edward R., Copeland Diane P., Cheng Seng H., Scheule Ronald K., Marshall John
Primary Institution: Genzyme Corporation
Hypothesis
Can iminosugar-based inhibitors of glucosylceramide synthase improve outcomes in a mouse model of Sandhoff disease?
Conclusion
Iminosugar-based inhibitors increased brain glycosphingolipids but still improved motor function and extended the lifespan of Sandhoff mice.
Supporting Evidence
- Treatment with Genz-529468 and NB-DNJ significantly increased the lifespan of Sandhoff mice.
- Both drugs delayed the loss of motor function and coordination in treated mice.
- Unexpected increases in brain glucosylceramide levels were observed despite improved outcomes.
Takeaway
Researchers gave special medicine to sick mice and found that it helped them live longer and move better, even though it made some bad stuff in their brains go up.
Methodology
Mice were treated with Genz-529468 or NB-DNJ, and their motor function, glycosphingolipid levels, and survival were assessed.
Potential Biases
Potential conflicts of interest due to authors' affiliations with Genzyme Corporation.
Limitations
The study was conducted in a mouse model, which may not fully replicate human disease.
Participant Demographics
Sandhoff mice, a model for human Sandhoff disease.
Statistical Information
P-Value
p<0.0001
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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