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Fenoterol and Fenoterol Analogues for Treatment of Glioma, Glioblastoma, and Astrocytoma

Posted Sep 08 2010 5:00pm

Description of Invention:
To date there is no effective treatment for the brain tumors or brain cancers indentified as gliomas, glioblastomas, or astrocytomas.

This technology relates to the discovery that fenoterol and related analogues block astrocytoma and glioblastoma cell division at low doses. In a xenograft model utilizing the 1321N1 astrocytoma tumor implanted in the flank of SKID mice, the (R,R)-4-methoxyfenoterol analogue significantly decreased tumor growth relative to a control group receiving vehicle and studies utilizing [3H]-(R,R)-4-methoxyfenoterol have shown that the compound readily passes the blood-brain barrier. The anti-tumor effect is associated with the ability of fenoterol and related analogues to induce production of cyclic adenosine monophosphate (cAMP), which is normally decreased in glioblastomas and astrocytomas. Induced cAMP production inhibits brain tumor growth in vivo. Fenoterol and related analogues are beta-2 adrenergic receptor (beta2 AR) agonists and the anti-tumor effect is associated with the expression of this receptor. Since there is a heterogeneous expression of beta2 AR in human brain tumors, patients who will respond to fenoterol therapy can be predetermined leading to individualized treatment. In addition to use in the initial treatment of brain tumors, the systemic and CNS bioavailability of the drug after oral administration and the minimal systemic toxicity suggest that fenoterol and it analogs can be used in the adjuvant treatment of patients with beta2 AR-positive gliomas, glioblastomas or astrocytomas. Studies with a number of fenoterol analogs and CNS-implanted tumors are in progress.

The fenoterol analogues discussed in this technology are subject to HHS Ref. No. E-205-2006/3 (U.S. Patent Application No. 12/376,945 and PCT Publication No. WO/2008/022038 ).

Applications:
Therapeutic in the front line and adjuvant treatment of glioma, glioblastoma and astrocytoma.

Advantages:
Potential first-in-class therapeutic for multiple types of brain tumors.

Development Status:
In vivo: tumor models in SKID mice. In vitro: cell-based assays using human glioblastoma and astrocytoma cell lines. Further in vivo studies in animal models are underway.

Inventors:
Irving W Wainer (NIA)


Patent Status:
HHS, Reference No. E-013-2010/0
US, Application No. 61/312,642 filed 10 Mar 2010


Relevant Publication:
  1. Submitted


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Institute on Aging, Laboratory of Clinical Investigation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of fenoterol and fenoterol analogs in the front line and adjuvant treatment of CNS tumors and other beta2 AR expressing tumors. Please contact Nicole Darack, Ph.D. at 301-435-3101 or darackn@mail.nih.gov for more information. Click here to view the NIA collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Therapeutics



For Licensing Information Please Contact:
Fatima Sayyid MHPM
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 21,
Rockville, MD 20852
United States
Email: Fatima.Sayyid@nih.hhs.gov
Phone: 301-435-4521
Fax: 301-402-0220


Ref No: 2160

Updated: 09/2010

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