Saturday, 9 January 2016

Cladribine

Cladribine (trade names Leustatin, Litak and Movectro) is a drug used to treat hairy cell leukemia (HCL, leukemic reticuloendotheliosis) and multiple sclerosis. Its chemical name is 2-chlorodeoxyadenosine (2CDA).

5-(6-Amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol

As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleosideadenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss.

Cladribine was designed by Dennis A. Carson as an anti-lymphocyte compound, while he was at The Scripps Research Institute in La Jolla, California. It was first synthesized at Brigham Young University.The pharmacology and clinical applications were researched by scientists at Johnson and Johnson, which filed the New Drug Application and launched the drug in 1993.

Cladribine was designed based on information about an immune deficiency disease called adenosine deaminase deficiency. Carson described it as "a targeted agent directed against lymphocytes at a time when there was no such thing as targeted agents".

In 2008, Ernest Beutler of The Scripps Research Institute won the Wallace H. Coulter Award for Lifetime Achievement in Haematology from the Coulter Foundation and theAmerican Society of Hematology in part because of the clinical trials he ran, which established cladribine as the most effective treatment for hairy cell leukemia (HCL).

20 comments:

  1. I'm curious: why did you post this? what is its relevance to ms treatment today?

    ReplyDelete
    Replies
    1. Wait and see, next week is cladribine week, as the Panorama programme on HSCThas been put back by another week

      Delete
    2. In an Era with a plethora of immunosupressants for ms treatments there is no room for Clabridine. Maybe it could have been the first Oral MS drug, but Team G blew it with their sloppy work. It's no wonder Charcot 1 failed.

      Give it up, Clabridine is dead.

      Delete
    3. Re: "Give it up, Clabridine is dead."

      Cladribine is far from dead. Merck-Serono are resubmitting the data package to the EMA to get it licensed in Europe. We and many other are using it in day-to-day practice, albeit off-label, to treat active MS. We are working with with our colleagues in resource poor-settings so they can offer it to pwMS with active disease who can't afford high-cost drugs. And DrK is in the process of trying to get a cladribine, combination therapy, trial off the ground in progressive MS. How can you say it is dead. It is live and kicking and making a difference to pwMS.

      Delete
    4. I'm glad it's being used off label in resource poor countries, but as an approved therapy for ms, the market is saturated with immunosupressants. How many more drugs of these class can the market bear? The cash cow is drying up for this approach as it should. If this is the case hopefully research will focus on a cure.

      Delete
    5. The Market is saturated...with ineffective treatments and effective treatments with serious side effects add to this expensive too. So should people not try to improve on this surely if there is a real market then this should happen. Who knows the cure could be there, but until neuros and pwMS stamp on Ms when it first rears its ugly head then we are wasting opportunities. Furthermore If MS is autoimmune the first part of the cure is immune depletion and alemtuzumab is not the answer.

      Delete
    6. Once the cash cow dries, big pharma will be off to the next pasture and that may not be to neuroprtection and repair and you may be stuck with what you have now.

      Word on the street is that some are already out of MS.

      Delete
    7. "Team G blew it with their sloppy work". Why the insults you are talking mushroom food. The failure of movectro lies in the hands of Merck. It was they that did only one trial and I guess the regulators must take part in this culpabilty too as they surely must have led merck to believe that one was OK. however the side effects meant that the regulators wanted more trials. Merck was too subborn to do them.

      Delete
    8. http://www.medscape.com/viewarticle/738239

      "The FDA decision is the latest in a long line of disappointment for the new drug in the race for first oral agent for MS. Cladribine was initially granted fast-track status by the FDA in 2006, but the agency refused to file the company's new drug application in 2009 amid speculation about tabulation errors and potential safety concerns."

      Merck was responsible for the tabulation errors? It sounds like it was a shodilly run trial. I guess maybe Merck chose the wrong group of researchers to handle a multi-billion dollar trial.

      Delete
    9. I'm pleased you are making full use of your freedom of speech. But it is nonsense to single out ProfG or any of his team as responsible for this rejection in 2010/11.

      Delete
    10. "Merck chose the wrong group of researchers to handle a multi-billion dollar trial".

      I doubt the trial cost multi-billion and so I wonder about the facts..when you sling mud you need to get these right or it one can end up in hot water.

      You need to understand that there is a team of people employed by pharma (Maybe Pharma or more likely outside contractors) to monitor and write up the regulatory documents. Academics don't generally know what is needed, so you accusations are unfounded.

      The data is the data, the interpretation is up for debate. Had Merck got there first and fingolimod did not happen the story may have been different, but it didn't.

      As to tabulation errors I suspect the proverbial "dead in a ditch" occurred for that person and they were probably fired and now work for one of the competitors:-) Or was it industrial espionage as we all like a conspiracy theory:-)

      Delete
    11. Regardless, the trial was a failure and you missed out for your spot in the sun. When Fingolomod goes generic Clabradine or any patentable derivative will be DOA.

      If you don't like me slinging mud maybe you should take a look at your arrogant behavior as your approach to this blog. If you can't take it don't dish it out.

      Delete
    12. The trial was not a failure, it gave a result and it is what it is. Remember the compound was licensed in Australia and Russia it may well be in Europe if Merck submits their documents to the EMA and they approve them.

      However if the FDA and EMA had approved Movectro, I am not sure I would have been in the sun as I was no part of the programme, not sure what you are getting at.

      "When Fingolimod goes generic, cladribine or any patentable derivative is Dead on Arrival".

      It depends on how they stack up, if they are better then maybe people will pay for them.

      Can we look forward to the day that fingolimod goes generic (although I am not sure when that is. The landscape may indeed change. Is it 2019 in US? Have Novartis lost on the 2026 extension case?. What about Australia?)

      You can sling mud if you like, but it helps if know why you are slinging it and it helps if you are right to sling it, otherwise you come across as a troll.

      What behaviour would you like changing?

      However, what I would like to understand is What position are you trying to defend and why? and what upsets you the most?

      Maybe get yourself a name like "Mudslinger" rather than hide behind anaonymous and we can dish the dirt:-)

      Delete
    13. Maybe the troll is the mom of a researcher who you upset MD.

      Delete
    14. LOL. was that because we reviewed their paper or didn't review their paper ;-).
      I guess if you want your info wrapped up in sugar and spice then I have decided not to do this. You can get that type of guff elsewhere

      If you dont agree you dont have to read. You may have an alternative view and you can call us on it if not done in a confrontational way.







      Delete
    15. This quote is useful in response to some of the comments we get.
      “Anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that 'my ignorance is just as good as your knowledge.'” ― Isaac Asimov

      Delete
    16. Anon 4.46 said
      "Insult.....Keep up the good work Team G".

      Thanks your support:-) but your comments are going into spam. We can do without your insulting behaviour. So bye now. Hugs & Kisses:-)

      You said "Why not just filter comments....blah blah blah..insult" Good call.. yours is spam, we are fed up with your endless wittering.

      Delete
  2. What did you learn from charcot 1? Have you looked at the effect of antiviral on people taking different DMTs? I am asking because if antivirals (contrary to a DMTs) do no affect virus in cells' DNA and that DMTs (contrary to antivirals) do not affect circulating virus then DMT + antivirals would get rid of circulating and sleeping viruses. No?

    ReplyDelete
    Replies
    1. What did I learn from Charcot 1....Keep quiet.....as you are cruising for a bruising if you open your mouth. Next raltegrovir was not a good choice.

      As to anti-viral effects of DMT I have no idea but Charcot is not my project.

      Delete
  3. Hello everyone,

    I am a MS patient and my doctor recently started injecting me with Cladribine.

    There will be 6 injections in cycle one, month apart, depending on my WBC count.

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.