Novel Tocopherol and Tocopheryl Quinone Derivatives as Therapeutics for Lysosomal Storage Disorders

Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes. These molecules by themselves or in combination with Cyclodextrins (CDs) increase intracellular Ca2+ and enhance exocytosis. Also, the treatment with these compounds reduced the pathological changes in the ultrastructure of LSD cells as observed using electron microscopy analysis. The inventors also found that there is a synergy between CDs and the new tocopherol analogues when tested on the NPC cells and cells from six other lysosomal storage diseases including Wolman, Niemann Pick Type A, Farber, TaySachs, MSIIIB and CLN2 (Batten) diseases. These new tocopherol analogues are as good or better than natural occurring tocopherols and tocotrienols in reducing cholesterol accumulation in several LSDs.

Potential Commercial Applications: Competitive Advantages:
  • To develop new therapeutics to treat LSDs.
  • The main advantage of the compounds disclosed here is their improved pharmacokinetics.
  • The combination of CD and the novel tocopherol analogues may reduce the dosage of each drug and thereby reduce the potential side effects.

Development Stage:
  • Prototype
  • Early-stage
  • Pre-clinical
  • In vitro data available

Related Invention(s):


Wei Zheng (NCATS)  ➽ more inventions...

Juan Marugan (NCATS)  ➽ more inventions...

John McKew (NCATS)  ➽ more inventions...

Jingbo Xiao (NCATS)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 9,663,485 issued 2017-05-30
U.S. Pat: 10,370,348 issued 2019-08-06
US Application No. 14/442,637
US Application No. 15/608,753

Collaboration Opportunity:

The National Center for Advancing Translational Sciences (NCATS) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Novel Tocopherol and Tocopheryl Quinone Derivatives as Therapeutics for Lysosomal Storage Disorders. For collaboration opportunities, please contact the NCATS Technology Development Coordinator at

Licensing Contact:
Suryanarayana Vepa, Ph.D.
Phone: 301-827-7181

OTT Reference No: E-148-2012-0
Updated: Mar 22, 2018