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

Posted Apr 22 2013 8:00pm

Description of Invention:
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.

Applications:
To develop new therapeutics to treat LSDs.

Advantages:
  • 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 Status:
  • Prototype
  • Early-stage
  • Pre-clinical
  • In vitro data available


Inventors:
Wei Zheng (NCATS)
Juan J Marugan (NCATS)
John C McKew (NCATS)
Jingbo Xiao (NCATS)


Patent Status:
HHS, Reference No. E-148-2012/0
US, Application No. 61/727,296 filed 16 Nov 2012


Related Technologies:
PCT, Application No. PCT/US2011/044590 filed 19 Jul 2011, Reference No. E-294-2009/0
US, Application No. 13/810,774 filed 17 Jan 2013, Reference No. E-294-2009/0
US, Application No. 61/679,668 filed 03 Aug 2012, Reference No. E-050-2012/0
US, Application No. 61/365,712 filed 19 Jul 2010, Reference No. E-294-2009/0


Collaborative Research 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 NCATSPartnerships@mail.nih.gov .


For Licensing Information Please Contact:
Suryanarayana Vepa Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vepas@mail.nih.gov
Phone: 301-435-5020
Fax: 301-402-0220


Ref No: 2554

Updated: 04/2013

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