Presumably GRN163L affects all stem cells. What will it do to non-cancer stem cells? Will new blood cells eventually cease to develop? Maybe they divide infrequently enough that the effect is small during the treatment period? Here are two interesting articles from PubMed found by searching for "telomerase inhibition".
Jason
Exp Gerontol. 2006 Jun 28; [Epub ahead of print]
Telomerase as a clinical target: Current strategies and potential applications.
* Fleisig HB,
* Wong JM.
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Chromosome ends are capped by telomeres, protective DNA-protein complexes that distinguish natural ends from random DNA breaks. Telomeres erode with each successive cell division, and such divisions cease once telomeres become critically short. This proliferation limit is important as a tumor suppressive mechanism, but also contributes to the degenerative conditions associated with cellular aging. In cell types that require continuous renewal, transient expression of telomerase delays proliferation arrest by the de novo synthesis of telomere repeats. Data from our work and others' has shown that deficient telomerase activity has a negative impact on normal human physiology. In the bone marrow failure syndrome dyskeratosis congenita, telomerase enzyme deficiency leads to the premature shortening of telomeres. Premature telomere shortening most grievously affects tissues that have a rapid turnover, such as the hematopoietic and epithelial compartments. In the most severe cases, compromised renewal of hematopoietic stem cells leads to bone marrow failure and premature death. Telomerase activation/replacement shows potential as a therapy for telomere maintenance deficiency syndromes, and in tissue engineering for the degenerative conditions that are associated with normal aging. Conversely, clinical researchers are developing telomerase inhibition therapies to treat tumors, which overcome the short-telomere barrier to unrestricted proliferation by over-expressing telomerase.
PMID: 16814507 [PubMed - as supplied by publisher]
-----------------------------------
Rejuvenation Res. 2006 Fall;9(3):378-90.Click here to read Links
Targeting telomerase.
* Siddiqa A,
* Cavazos DA,
* Marciniak RA.
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Given the constitutive expression of telomerase in the majority of human tumors, telomerase inhibition is an attractive, broad-spectrum therapeutic target for cancer treatment. Therapeutic strategies for inhibiting telomerase activity have included both targeting components of telomerase (the protein component, TERT, or the RNA component, TERC) or by directly targeting telomere DNA structures. Recently a combination telomerase inhibition therapy has been studied also. The TERT promoter has been used to selectively express cytotoxic gene(s) in cancer cells and a TERT vaccine for immunization against telomerase has been tested. The 10% to 15% of immortalized cancer cells that do not express telomerase use a recombination-based mechanism for maintaining telomere structures that has been called the alternative lengthening of telomeres (ALT). In view of the increasing study of telomerase inhibitors as anticancer treatments, it will be crucial to determine whether inhibition of telomerase will select for cancer cells that activate ALT mechanisms of telomere maintenance.
PMID: 16859479 [PubMed - indexed for MEDLINE] |
