Treatment of Acute and Chronic Neurological Disorders Using GLP-1, Exendin-4 and Analogs


Glucagon-like peptide-1 (GLP-1) and related peptides, including exendin-4 and liraglutide, are incretin mimetics that enhance glucose-dependent insulin secretion following food ingestion as a regulator of glucose homeostasis. Exendin-4 and liraglutide are used clinically in the safe and effective treatment of type 2 diabetes to enhance insulin secretion and maintain a euglycemic state. These actions are primarily mediated at the level of the GLP-1 receptor in the pancreas; however, these compounds are known to enter the brain where the GLP-1 receptor also is expressed.

Researchers at the NIH have discovered the novel use of GLP-1 and exendin-4 analogs in the treatment of acute and chronic neurological disorders and neurodegenerative diseases. Studies conducted in extensive cell culture and in mouse models using these analogs have demonstrated significant neurotrophic and neuroprotective actions in models of several disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS, stroke, head trauma and peripheral neuropathy. These studies have now been extensively published and independently validated by other scientific groups. Furthermore, clinical studies are ongoing to evaluate the use of GLP-1 receptor agonists for the treatment of early Alzheimer's disease, Parkinson's disease and diabetic neuropathy by several groups within the US and Europe.

Potential Commercial Applications: Competitive Advantages:
Therapeutics for:
  • Neurodegenerative diseases – Alzheimer’s, Huntington’s, Parkinson’s, ALS
  • Stroke
  • Head trauma (traumatic brain injury)
  • Peripheral neuropathies
 
  • Compounds reduce neuronal cell death, amyloid deposition and neuroinflammation while promoting neurogenesis.
  • Compounds in this class have already been shown to be safe and effective for other indications.
  • Extensive in vitro and animal data are available, and clinical studies are ongoing.
  • There are extensive publications in the literature, both from the inventors and independent groups.


Development Stage:
  • Pre-clinical
  • Clinical
  • In vitro data available
  • In vivo data available (animal)
  • In vivo data available (human)


Inventors:

Josephine Egan (NIA)  ➽ more inventions...

Harold Holloway (NIA)  ➽ more inventions...

Maire Doyle (NIA)  ➽ more inventions...

Nigel Greig (NIA)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 8,853,160 issued 2014-10-07
U.S. Pat: 7,576,050 issued 2009-08-18
U.S. Pat: 8,278,272 issued 2012-10-02
US Application No. 12/317,042
PCT Application No. PCT/US02/24141
US Application No. 14/470,528
and foreign counterparts in Australia, Canada, Europe, India, and Japan

Publications:
Li Y, et al. PMID 22384126
Li Y, et al. PMID 20374430
Li Y, et al. PMID 20308787
Li Y, et al. PMID 19164583
Martin B, et al. PMID:18984744
Perry T, et al. PMID 17125767
Perry T, Greig NH. PMID 15974903
Greig NH, et al. PMID 15681814
Perry TA, Greig NH. PMID 15270203
A listing of additional related publications is available upon request.

Collaboration Opportunity:

The National Institute on Aging, Drug Design and Development Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Vio Conley at conleyv@mail.nih.gov.


Licensing Contact:
Charlotte McGuinness, Ph.D., J.D.
Email: cm432k@nih.gov
Phone: 240-276-5530

OTT Reference No: E-049-2001/0
Updated: Oct 5, 2015