It is huge medical news that you won't read about in the press, and it illustrates the power of Geron's first in man telomerase inhibitor. It attacks an enzyme required for the stem cell-ish nature of cancer stem cells.

In this case, it's little matter that the study is in rodents. What is incredible is that with a very short, less than optimal treatment period (too short), they doubled survival time for brain cancer in rodents, AND THEY DID IT WITHOUT A DIRECT INFUSION TO THE BRAIN, WITHOUT A TOXIC SMALL MOLECULE, AND THEY DID IT WILL NASAL DROPS. This means that any cancer that has spread to the brain is reachable easily with GRN163L. Its massive news!!! It also illustrates the importance of getting far better air pollution laws in the world. What we breathe goes to our brain directly in many cases, bypassing the blood brain barrier. That is why immune system/blood brain disorders are the most often diagnosed disease in the U.S.

as you read this consider that the rodents were given a short treatment, not long enough to cure them. Multiiple human trials are ongoing with I.V. administration of the drug. Humans are getting the drug for months right now,(not for only 12 days like these unlucky rodents) via I.V., for many human cancers. Trial info at www.geron.com click on patient info on the left for trial site contact information. Nasal administration of the drug means the ability to treat cancers that originate or have spread to the brain, without side effects(citing other studies of the drug).
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First published on February 20, 2008
This version was published on April 1, 2008
Neuro Oncol 2008 10(2):112-120; DOI:10.1215/15228517-2007-052
Articles by Hashizume, R.
Articles by Deen, D. F.


PubMed Citation

Duke University Press

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Basic and Translational Investigations

New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163
Rintaro Hashizume, Tomoko Ozawa, Sergei M. Gryaznov, Andrew W. Bollen, Kathleen R. Lamborn, William H. Frey, II and Dennis F. Deen
Brain Tumor Research Center of the Department of Neurological Surgery, University of California San Francisco, San Francisco, CA (R.H., T.O., K.R.L., D.F.D.); Geron Corporation, Menlo Park, CA (S.M.G.); Department of Pathology, University of California San Francisco, San Francisco, CA (A.W.B.); Alzheimer's Research Center, HealthPartners Research Foundation at Regions Hospital, St. Paul, MN (W.H.F.); USA

Address correspondence to Rintaro Hashizume, Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143-0520, USA (rintaro.hashizume@ucsf.edu ).

The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are greatly needed for brain-tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain and could provide an alternative to intravenous injection and convection-enhanced delivery. We treated rats bearing intracerebral human tumor xenografts intranasally with GRN163, an oligonucleotide N3'P5'thio-phosphoramidate telomerase inhibitor. 3'-Fuorescein isothiocyanate (FITC) - labeled GRN163 was administered intranasally every 2 min as 6 µl drops into alternating sides of the nasal cavity over 22 min. FITC-labeled GRN163 was present in tumor cells at all time points studied, and accumulation of GRN163 peaked at 4 h after delivery. Moreover, GRN163 delivered intranasally, daily for 12 days, significantly prolonged the median survival from 35 days in the control group to 75.5 days in the GRN163-treated group. Thus, intranasal delivery of GRN163 readily bypassed the blood-brain barrier, exhibited favorable tumor uptake, and inhibited tumor growth, leading to a prolonged lifespan for treated rats compared to controls. This delivery approach appears to kill tumor cells selectively, and no toxic effects were noted in normal brain tissue. These data support further development of intranasal delivery of tumor-specific therapeutic agents for brain tumor patients.

Key Words: brain tumors • GRN163 • intranasal delivery • telomerase inhibitor • xenografts

Copyright 2008 by Society for Neuro-Oncology