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Lenalidomide Analogs for the Treatment of Neurodegenerative Disorders and Cancer

Posted Mar 22 2012 8:00pm

Description of Invention:
Inflammatory processes associated with the over-production of tumor necrosis-alpha (TNF-alpha), a potent activator of the immune system accompany numerous neurodegenerative diseases. TNF-alpha has been validated as a drug target with the development of the inhibitors Enbrel and Remicade (fusion antibodies) as prescription medications. Both, however, are large macromolecules that require direct injection and have limited brain access. The classical drug, thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. The NIA inventors developed and assessed novel thio analogs of lenalidomide (Celegene's Revlimid and an analog of thalidomide) as immunomodulatory agents, with the potential to reduce chronic systemic and central nervous system inflammation. These compounds were synthesized and evaluated for their TNF-alpha inhibitory activity. This invention was extended from the inventors' prior work to develop potent compounds to reduce neuroinflammation as a treatment strategy for neurodegenerative disorders. The current studies focus the compounds activity in classical models of neurodegeneration as well as cancer.

Applications:
  • Treatment for blood disorders (myelodysplastic syndrome), cancer (multiple myeloma), inflammatory processes and erythema
  • Immunomodulatory agents
  • Reduce chronic systemic and central nervous system inflammation


Advantages:
  • Effective smaller molecular weight compound that can enter brain among current agents
  • Experimental therapeutic to reduce inflammation systematically and within the brain
  • Effective in reducing proinflammatory cytokines than existing agents


Development Status:
  • Prototype
  • Clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Harold W Holloway (NIA)
Qian-sheng Yu (NIA)
Nigel H Greig (NIA)
Weiming Luo (NIA)
David Tweedie (NIA)


Patent Status:
HHS, Reference No. E-045-2012/0
US, Application No. 13/310,242 filed 02 Dec 2011


Related Technologies:
US, Patent No. 7,973,057, Issued 05 Jul 2011, Reference No. E-189-2003/0
US, Application No. 13/153,355 filed 03 Jun 2011, Reference No. E-189-2003/0
US, Application No. 60/504,724 filed 17 Sep 2003, Reference No. E-189-2003/0


Relevant Publication:
  1. Luo W, et al. [ PMID 21658960 ]



For Licensing Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 2389

Updated: 03/2012

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