The first telomerase inhibitor in trials

[Birgitta-A]

Hi All,
Now they are reporting trials with the first telomerase inhibitor called Imetelstat. They try the drug on patients with two hematological cancers - Essential Thrombocythemia and Multiple Myeloma. You have to register.
http://jpmorgan.metameetings.com/web...hp?ticker=GERN
Kind regards
Birgitta-A

[triumphe64]

Originally Posted by Birgitta-A

Hi All,
Now they are reporting trials with the first telomerase inhibitor called Imetelstat. They try the drug on patients with two hematological cancers - Essential Thrombocythemia and Multiple Myeloma. You have to register.
http://jpmorgan.metameetings.com/web...hp?ticker=GERN
Kind regards
Birgitta-A

This fights cancer cells, but would hurt those of us who want our normal telomeres to grow longer. Correct? That means they need a way to target the cancer cells.

[Birgitta-A]

Hi triumphe64,
As far as I understand a drug that inhibits telomerase should lead to that all telomeres can stay long. Here is an article - perhaps Greg has already posted it - about telomerase inhibitors. They write: However, the long-term effects of regulating telomerase either positively or negatively are unclear. It is possible that inhibition of telomerase could have adverse side effects on normal stem cell function and immune response as stem and immune cells have increased telomerase activity to accommodate frequent proliferation. http://onlinelibrary.wiley.com/doi/1...11.01460.x/pdf
Kind regards
Birgitta-A

[Greg H]

Hi Birgitta & Triumph!

Wow! This is complicated, isn't it? The article Birgitta posted is excellent, though it can be a tough read because of a lot of technical language.

Here's how I understand telomeres, telomerase, their inhibition and activation, and the paradoxical way all that relates to bone marrow failure.

Normally, human cells (and animal cells) can only divide some many times before they shut themselves down and eventually die. This is called the "Hayflick limit," named after the scientist who discovered it. Some folks think this limit is a key reason that we humans, and all animals, age.

What triggers the Hayflick limit and cell death is the gradual shortening of telomeres -- little nonsense clusters of proteins on the ends of chromosomes. When a cell divides, and its chromosomes duplicate themselves, the telomeres are there to make sure the cell divides at the right spot, so some chunk of DNA doesn't get torn off and put back where it doesn't belong. When a cell's telomeres get too short, it shuts down, quits reproducing, and eventually dies.

But some cells in the body need to divide a lot. Bone marrow stem cells, for example, have to produce many, many blood cells every day. So they can't put up with the Hayflick limit. Their telomeres need to be repaired and re-lengthened after ever cell division. That is the job of telomerase, a complicated substance that works complicated magic and lengthens the telomeres on the ends of bone marrow stem cells after every division -- so they can keep dividing and making more blood cells.

I have a genetic mutation that messes up part of the telomerase cycle. That means my stem cells have too-short telomeres and are not very effective at producing blood cells. I could use some telomerase activation to help this process, which is why I'm taking Danazol.

But here's a fascinating thing about a lot of cancers: many tumor cells are "immortal." They refuse to die like normal cells; they thwart the Hayflick limit and keep dividing. How do they do this? By exploring the telomerase cycle. These tumor cells use telomerase to keep themselves dividing and keep the tumor growing.

So, there's a lot of hope that some solid tumor cancers can be combatted by targeting the telomerase cycle. For example, you could have a drug that inhibited telomerase, taking away this tool that the cancer uses to grow. Or you could find a drug that recognizes cells using telomerase and kills them.

The article that Birgitta posted talks about both these possibilities, either of which could be useful, depending on whether you have prostate cancer or bone marrow failure.

But, as it says, there are a lot of unknowns. What if you give someone a telomerase inhibitor to shrink their prostate cancer and it has the side effect of suppressing red blood cell production in their bone marrow? Or, what if you give someone an injection of a telomerase activator to give them younger-looking skin, and that inadvertently activates a latent skin cancer?

It's all very complicated -- and really, really interesting.

Hope that's useful! I'm going to go read the articles on how Geron's drug is being used in myeloma and leukemia. I'll report back.

Greg

[Greg H]

Hi All!

I've been doing some more thinking about the article Birgitta posted on telomerase inhibition and activation.

One section of the article lists a variety of "natural" substances that contain phytochemicals that seem to have some ability to inhibit telomerase: garlic, curcumin, EGCG (the active ingredient in green tea), soy, reservatrol (from red wine).

Now, if you're like me, once you figured out that MDS can be classified as a cancer, you went out and started reading up on things you could do -- in addition to following your doctor's advice -- to improve your odds of fighting the disease. I read "Anti-Cancer," by David Servan-Schreiber, which helpfully explained how a lot of these substances can contribute to the death of cancer cells. So, I developed a taste for green tea.

But, as it turns out, that green tea may be useful as a cancer-fighter mostly because it messes up the telomerase cycle. And the kind of MDS I have may be the result of a messed up telomerase cycle.

Now, I'm not suggesting green tea gave me MDS. I never knowingly ingested green tea until after I was diagnosed. But its an interesting example of how some "natural" remedy that's good for one kind of cancer might not be the right choice for another.

Our diseases, cancer, MDS, AA, PNH, are, it turns out, all unique and pretty darned complicated. And that can make it pretty tricky to decide what strategies to use to try to heal yourself.

Take care!

Greg

[Birgitta-A]

Hi Greg,
Yes the ways natural substances eventually work are really very complicated:

Several compounds have been shown to act as both inhibitors and activators of telomerase though this may be due to treatment concentration or cell type differences...

For example a study about genistein (soybean) suggests it may activate telomerase activity at low concentrations and inhibit telomerase activity at higher treatment concentrations.

I have tried to find anything serious about wheatgrass but not seen anything I can post.
Kind regards
Birgitta-A

[Lbrown]

If you ask me (and I know you didn't ) these researchers can't see the forest for the trees because they are too busy trying to find some drug they can get to market and make $. I wish more research was done with less eyes on the bottom line, because I think research is missing the big picture.

Thanks for posting the article, I will definitely read it.

Deb

[Greg H]

Deb,

It's funny; I was talking about just this point with a friend the other day. It seems to me this is one reason that we in the US need to fund more NIH-style basic research and not just think "the market" is going to get us the answers we need.

Neither of the drugs that I've taken in NIH trials -- Campath (developed at a university lab in Great Britain) or Danazol (on the market since the 1970s) -- is going to make anyone any big money. So there's no profit in a drug company putting money into a trial that uses these drugs. We're only going to learn whether they are useful through research funded by governments, universities, and private foundations.

Here's another example. If you look through the ASH abstracts for MDS this year, there are probably a dozen or more studies that involve Exjade and none that involve wheatgrass. Why? Novartis stands to make money by broadening the market for Exjade and is trying to convince skeptical MDS docs that chelation is worth the expense. No one with substantial resources has a financial interest in the expansion of the wheatgrass trade.

Take care!

Greg

[Birgitta-A]

Hi Deb and Greg,
Yes, there is only one trial about wheatgrass at clin trials gov and that is for fatigue. The only trial about curcumin in MDS patients was withdrawn due to lack of funding.
http://clinicaltrials.gov/ct2/show/N...min+mds&rank=1
Kind regards
Birgitta-A

[cathybee1]

This is such an interesting thread...I hope the testing for telomeres becomes more readily available. And Greg, you are spot on regarding pharmaceutical lobbying in this country.

[Lbrown]

Hi guys,

Thanks for making me not feel like a medical heretic, lol. I couldn't agree with you more.

I do hate wheatgrass, but I hate exjade more. I didn't give wheatgrass a fair try though. The pills my husband bought me tasted gross - my horse might like them though.

Circumin is supposed to be a VDR agonist, which is the idea behind the treatment I'm on (using olmesartan as the VDR agonist). Olmesartan is not that expensive and is almost off patent. I believe Sankyo got an extension until 2016. There's lots of fairly new research on using VDR agonists, only problem is a lot of them are toxic (as is 1,25D in larger doses, which is the endogenous VDR agonist). Unfortunately, olmesartan seems infuriatingly slow-acting. I bet there'd be NO money in curcumin. Maybe for the grocery store.

Don't know if this is the right place for this, but I just found this article, they mention MDS as well as other diseases, and I am into the infection model of disease:

Ehrlichia and bone marrow cells: could Ehrlichial infection explain the unsuspected etiology of some diseases of the immune system?
http://www.ncbi.nlm.nih.gov/pubmed/21669495

Deb

[Greg H]

Hey Deb!

If you decide to give wheatgrass another shot, you could try the capsules of freeze-dried wheatgrass juice from Eclectic Institute. The capsules are about the size of a Tylenol caplet, so they aren't hard to swallow and they taste like nothing.

I've been using those, but I've also ordered some more of the "horse" pills, which appear to be ground up wheatgrass stuck together with some kind of a binder. I actually got to like the taste of those. Go figure!

I've tried the wheagrass powder in smoothies, but I'm not being good about making the smoothies everyday, so I figure the pills and tablets are going to work better for me.

I don't expect to know whether the wheatgrass has helped for a couple more months, when I'll get my ferritin checked again. I really hope I can use it to avoid Exjade, but that may be a pipe dream.

Thanks for the article. I'm going to go read it now.

Take care!

Greg

[Lbrown]

My wheatgrass was some sort of ground up pills too. Yuck. $41 and you had to take 7 a day. I am thinking if it really DID chelate iron, it would kill a normal person! I shouldn't complain though because my husband picked them out and I never gave him any details to go on.

Tasteless sounds good. I must look that up.

Thanks,
Deb