Available Technology

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

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 growthin 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-205-2006/2(US Patent No.8,703,826).
Abstract: 
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 growthin 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-205-2006/2(US Patent No.8,703,826).
Benefits: 
Potential first-in-class therapeutic for multiple types of brain tumors.
applications: 
Inventors: 
Irving Wainer (NIA)
Patent Number: 
61/312,642 PCT Application No. PCT/US2011/027988 U
Internal Laboratory Ref #: 
E-013-2010/0
Lab Representatives
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