Substrate Reduction Therapy for Sandhoff Disease through Inhibition of Glucosylceramide Synthase Activity.

@article{Marshall2019SubstrateRT,
  title={Substrate Reduction Therapy for Sandhoff Disease through Inhibition of Glucosylceramide Synthase Activity.},
  author={John Marshall and Jennifer B. Nietupski and Hyejung Park and James Cao and Dinesh S. Bangari and Cristina I. Silvescu and Terry Wilper and Kristen L. Randall and Drew R. Tietz and Bing Wang and Xiaoyou Ying and John P. Leonard and Seng H. Cheng},
  journal={Molecular therapy : the journal of the American Society of Gene Therapy},
  year={2019}
}
Neuronopathic glycosphingolipidoses are a sub-group of lysosomal storage disorders for which there are presently no effective therapies. Here, we evaluated the potential of substrate reduction therapy (SRT) using an inhibitor of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide (GL1) and related glycosphingolipids. The substrates that accumulate in Sandhoff disease (e.g., ganglioside GM2 and its nonacylated derivative, lyso-GM2) are distal to the drug target, GCS… 
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