Abstract
A fundamental limitation in the treatment of brain tumors is that < 1% of most therapeutic agents administered systemically are able to cross the blood-brain barrier (BBB). The development of new strategies that circumvent the BBB should increase the likelihood of tumor response to selected therapeutic agents. Intranasal delivery (IND) is a practical, noninvasive method of bypassing the BBB to deliver therapeutic agents to the brain. This technique has demonstrated promising results in the treatment of neurological disorders. Telomerase is a reverse transcriptase that is expressed in the vast majority of malignant gliomas, although not in the healthy brain. Telomerase inhibition can therefore be used as a therapeutic strategy for selectively targeting malignant gliomas. The first successful IND of a telomerase inhibitor as a therapy for brain tumors was GRN-163, an oligonucleotide N3'→5' thiophosphoramidate telomerase inhibitor, which was successfully administered into intracerebral tumors in rats with no apparent toxicity. GRN-163 exhibited favorable tumor uptake and inhibited tumor growth, leading to prolonged lifespan in treated animals. The IND of telomerase inhibitors represents a new therapeutic approach that appears to selectively kill tumor cells, without inducing toxic effects in the surrounding healthy brain tissue.
Original language | English (US) |
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Pages (from-to) | 168-175 |
Number of pages | 8 |
Journal | Current Opinion in Molecular Therapeutics |
Volume | 12 |
Issue number | 2 |
State | Published - Apr 2010 |
Keywords
- Blood-brain barrier
- Brain tumor
- GRN-163
- GRN-163L
- Imetelstat
- Intranasal delivery
- Telomerase inhibitor
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery
- Genetics(clinical)