Lenalidomide Analogs for the Treatment of Neurodegenerative Disorders and Cancer


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.

Potential Commercial Applications: Competitive Advantages:
  • Treatment for blood disorders (myelodysplastic syndrome), cancer (multiple myeloma), inflammatory processes and erythema
  • Immunomodulatory agents
  • Reduce chronic systemic and central nervous system inflammation
 
  • Effective smaller molecular weight compound that can enter brain among current agents
  • Experimental therapeutic to reduce inflammation systematically and within the brain
  • More effective in reducing proinflammatory cytokines than existing agents


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


Related Invention(s):
E-189-2003/0


Inventors:

Harold Holloway (NIA)  ➽ more inventions...

Qian-sheng Yu (NIA)  ➽ more inventions...

Nigel Greig (NIA)  ➽ more inventions...

Weiming Luo (NIA)  ➽ more inventions...

David Tweedie (NIA)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 9,623,020 issued 2017-04-18
U.S. Pat: 8,927,725 issued 2015-01-06
U.S. Pat: 9,084,783 issued 2015-07-21
US Application No. 15/457,156

Publications:
Luo W, et al. PMID 21658960

Collaboration Opportunity:

This invention is available for licensing and co-development. Please contact John D. Hewes, Ph.D. at 240-276-5515 or john.hewes@nih.gov for information.


Licensing Contact:
Surekha Vathyam, Ph.D.
Email: vathyams@mail.nih.gov
Phone: 240-276-6865

OTT Reference No: E-045-2012/0
Updated: Dec 14, 2017