Published on August 26, 2014
Dr. David Snyder from City of Hope defines telomerase inhibitors and explains the research currently taking place to understand how these agents work to treat myeloproliferative neoplasms (MPNs).
This event was produced in association with City of Hope and sponsored by Patient Empowerment Network through educational grants from Incyte Corporation and Geron Corporation.
Transcript | MPN Treatments in Development: Telomerase Inhibitors
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Okay. Now you, Brian has been in a trial for, I think a telomerase inhibitor, I think it is.
A telomerase inhibitor.
So we talked about the JAK pathway and you mentioned that other genes and other pathways. Is that where that comes in?
Well, so let me talk about the telomerase a little bit. Anyone who has shoes on and shoelaces, I do, so this little plastic tip of your shoelace that’s called an aglet, and that helps to keep the shoelace from unraveling, all right?
So if you think about that as similar with a chromosome inside the cell, it’s complex strands of DNA and proteins together. And the end of the chromosomes are called telomeres, and those are like the aglets. It keeps the chromosome from unwinding, unraveling and falling apart.
So what happens normally as the lifetime of a cell as opposed to cell division, the length of this telomere gets shorter with each cell division and eventually gets so short that the chromosomes do fall apart, and the cell dies.
That’s one of the ways that cells with so-called programmed cell death. And with some cancers, some malignancies, it’s known that the activity of the enzyme called telomerase, which is an enzyme that reverses that process, it lengthens the telomere so the telomerase activity may be increased, and that may be a way for the cells to become immortal, if you will, to allow them to live.
And so along comes the drug, which is called Imetelstat, which is a telomerase inhibitor. So it interferes with the activity of that enzyme, that telomerase. Now, it’s been studied in a variety of conditions and for some early Phase I trials, and it was found to have some significant effects on lowering platelets in some patients.
And that led to a trial that we’ve been part of, that Brian’s been part of, for patients with ET. It was expanded then to patients with P. vera [polycythemia vera], and there also is a study being done to the Mayo Clinic in patients with myelofibrosis. There’s been a lot of encouraging results coming out of that. We can’t yet connect all the dots.
In other words, we know that Imetelstat is a telomerase inhibitor. It’s not yet known exactly how the drug works inside the cell in these conditions, but we do what the readout is, what the clinical benefit has been.
Okay, and we should say that this is being studied. There’s some ongoing trial at the Mayo Clinic. There’s been a trial here right now in ET that has been halted at this moment while the FDA is looking at effects on the liver because safety is always the number one concern.