August 2 2007 post. This morning a myeloma listserv member reported on something that he has been taking for the past two months called cyclopamine. I’d never heard of it before, or perhaps hadn’t paid any attention to it, so I looked it up. Well, this may be one of the most exciting things I have read about in recent times. I still have some (a lot of?) research to do, but I thought I would post some preliminary findings. I still have to read all of the following studies carefully when I have more time. Not today.
The remarkable story of how cyclopamine was discovered can be read in the following 2005 article published in Forbes: http://tinyurl.com/yu6df5 In a nutshell: in the 1940s and 50s, one-eyed lambs were being born on a farm in Idaho. During an 11-year investigation conducted by the U.S. Dept. of Agriculture, it was discovered that the farm’s sheep were grazing in fields of corn lilies, flowers that contain a poison (later called cyclopamine) that does not harm adult animals but does cause birth defects. The Forbes article provides many more details, also about how cyclopamine later came to be of interest to cancer research. Fascinating. Cyclopamine was found to inhibit a gene known as Sonic hedgehog, which is involved in the process of adult stem cell division and apparently is crucial for the development of myeloma, pancreatic cancer and other cancers. For more info on the importance of hedgehog pathways and myeloma and other B-cell malignancies, please see this July 2007 study: http://tinyurl.com/25w9or.
A team of researchers at Johns Hopkins made the connections between cyclopamine, the Idaho lambs and the hedgehog gene. Their findings were published in 2002 in Genes and Development (http://tinyurl.com/38vppa). A few years later, in 2006, a Stanford study published in PNAS tells us that the hedgehog signalling (or Hh) pathway is crucial for the proliferation of myeloma stem cells. Well, lo and behold, cyclopamine inhibits that pathway: http://tinyurl.com/2hx5yd.
As I mentioned, I have been able to glance only at the conclusions of all these studies, but plan to read them carefully soon. My time has run out, but I did want to post quickly about this bit of extraordinary news. If we can get rid of our cancer-making stem cells, we can kill off the remaining cancer cells with curcumin or resveratrol or whatnot. How about that? A couple of final questions (and this is another reason why I need to do more research!): how come cyclopamine targets only cancer stem cells? Why doesn’t it target non-cancerous stem cells as well?
August 3 post: A lot of interest on the myeloma listserv concerning cyclopamine. Rightly so, I might add. I am still poring over the scientific studies dealing with this topic, but some of the jargon is beyond my translating abilities. So this will take a bit of time (which I do not have, at present!). However, I did find out a couple of things, which may be of general interest.
1. cyclopamine is very expensive: one gram costs $ 5,000. I would be happy to provide more info to anyone interested (the company name, etc.). It appears that cyclopamine is sold in a powder (?) form, since there are warnings on how to store and handle it (wear gloves and a mask, etc.);
2. initially, the myeloma listserv member tested cyclopamine together with Revlimid and Dexamethasone (the latter: pulsing, every 4-5 weeks). He reports, though, that his M-spike had not decreased on the latter two drugs, which by then he had been taking for seven months. However, when he added a daily dose of 200-300 mg of cyclopamine (mixed in water) for ten days, his M-spike went from 0.9 to 0.4-0.5. His most recent self-administered cyclopamine test lasted 15 days, again at 200-300 mg/day. At that point he added lovastin, a cholesterol-lowering drug. The lovastin-cyclopamine combination, by the way, was tested in a research trial at Johns Hopkins (see the January 2007 Johns Hopkins press release: http://tinyurl.com/2m92jg). When administered together, they killed 63% of brain cancer cells; when used separately, that number went down to less than 20%. At any rate, on this combo, the list member’s M-spike went down to 0.3, and is now down to 0.2. Of course, as with curcumin (in my case), it is difficult to say whether or not it is the cyclopamine. My bet is on cyclopamine, though.
Anyway, the cyclopamine studies and the myeloma list member’s reports, are very promising. Yes, cyclopamine costs an arm and a leg, but taking out myeloma by its roots has always been my dream, and this may well be another (non toxic) step in the right direction.
Update February 21 2008 post: Yesterday a myeloma list member reported his test results after five cycles of cyclopamine. He authorized me to post about it.
Here are some details posted by the cyclopamine-taking list member (from now on, I will refer to him as CT, or cyclopamine-taker) took a water-soluble form of cyclopamine for a year and a half. More specifically, he took 200 mg of cyclopamine a day for 14-15 days at a time, every 2-4 months. His m-spike went from 1.0 (achieved after two stem cell transplants two and a half years ago) to 0.2, then to 0.1, and he is convinced that these decreases, the first since his transplants, were due to his cyclopamine intake. Coincidental? Possibly. He reported, by the way, no side effects. Indeed, he feels great.
Okay, but we should not get TOO excited about this substance. The main reason, at least as far as I am concerned, is that it costs an arm and a leg. I had the brilliant idea of seeing if I could order some and ask my parents bring it over to me when they fly to Italy for their regular summer visit, but when I saw what it cost, i.e. thousands of dollars, my eyes almost popped out of my head. No way I could afford it. CT has a cheaper source than what I found online, but it’s still way beyond my budget.
Another list member pointed out that he would be anxious about potential side effects that might not manifest themselves immediately, but perhaps 20 years down the road. But CT (good sense of humour!) said that he would be happy to survive 20 years with myeloma! Indeed. He added that he is well aware that there are possible risks involved in taking a substance that hasn’t been approved by the FDA, but after all, we are dealing with myeloma, not an ingrown toenail (my analogy, actually). So true.
CT reminded us that Dr. Matsui reported in April 2006 at the American Association for Cancer Research (AARC) meeting that cyclopamine caused differentiation of myeloma stem cells. In other words, the myeloma stem cells were eliminated because they did not produce any more cancer stem cells. The stem cells turned into mature plasma cells that eventually died out. Normal cells were not affected, he reported.
For an interesting Science Daily article (2002) on cyclopamine, see: http://tinyurl.com/2zcwut
In PubMed there are 260 studies on cyclopamine. But there is not one clinical trial. Typical.
As usual, I hope this situation will change soon. If it does, I might be first in line!
Update on the update: with this post, I wanted to report on an interesting case, perhaps (I hope!) a crucial one in the battle against myeloma stem cells. I would like to underline, though, that I am not encouraging folks to take cyclopamine. Even though we aren’t pregnant sheep (if you are puzzled about that statement, read my page on cyclopamine: all will be clear ), we still don’t know if there might be harmful side effects (etc.). CT did report that he had none, which is extremely important. In sum, I think this substance should definitely be put on our watch-and-see list. Yes, indeedie!
February 26 2008 update. Concerning water solubility, CT stated: I took cyclopamine tartarate which Logan labs claims is somewhat water soluble. Mice at UTMS took the regular cyclopamine orally for basal cell CA and it worked, so it must be getting absorbed. I note that is does mix well in water. In any event, my M-marker did go down. I will know more when I retest.