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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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June 9, 2011

Cardiac Hope and Cardiac Hype

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Posted by Derek

There have been quite a few headlines over the last few days like this one: "A New Drug Makes Hearts Repair Themselves". Unfortunately, that's not quite true. Not yet.

It's this paper in Nature that's getting the attention, and it is a very interesting one. The authors have identified a population of progenitor cells in the adult heart that can be induced to turn into fully differentiated myocytes after an infarction. In fewer syllables, and reasonably accurately: stem cells, already in the heart, can be made to repair it after a heart attack. And that's getting closer to that headline I was just complaining about - so what's the gap between the two?

Well, there are several rather huge factors. One of them is that the way that these cells were stimulated into action was by treatment with thymosin beta-4, which is a potent regulator of cardiac cells and blood vessel development. Tβ4 is not quite a drug yet, although RegeneRx is giving it a shot. There have been some phamacokinetic studies in animals and other preliminary work, and I wish them every good fortune. But it's got a ways to go.

Second, this study treated the animals with Tβ4 for seven days before inducing the cardiac injury. That's perfectly reasonable for a proof-of-concept study like this one, but it's not the real-world therapeutic option that you'd imagine from the press coverage. As one correspondent put it to me in an e-mail, "if you’re a mouse, and you know that later on this week you’re going to have an MI, then this is the treatment for you". That might be unfair to the original authors, who are working their way up carefully through some very tricky biology, but it's not unfair at all to the people who write headlines like the one I quoted above.

No, this is very interesting stuff, but it's quite a ways from being ready to help any of us out. This is where such therapies start, though, and we can only hope that something makes it through this time. The authors themselves know the score:

". . .The induced differentiation of the progenitor pool described into cardiomyocytes by Tβ4 is at present an inefficient process relative to the activated progenitor population as a whole. Consequently, the search is on via chemical and genetic screens to identify efficacious small molecules and other trophic factors to underpin optimal progenitor activation and replacement of destroyed myocardium.

Comments (5) + TrackBacks (0) | Category: Cardiovascular Disease | Press Coverage


COMMENTS

1. barry on June 9, 2011 11:42 AM writes...

if thymosinB-4 can prompt cells do differentiate, can it re-impose senescence on cancer cells? Since we have learned to make induced pluripotent stem cells and to prod them to differentiate, we have entered a new world of potential cancer modifiers and of carcinogenesis. I would imagine that the hurdle to approving such a treatment as a prophylactic will be sky-high. Even as a therapeutic post-MI it will be hard to demonstrate safety.

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2. Pete on June 10, 2011 12:35 AM writes...

As amazing as the advances in medical technology that occur on a daily basis are, it's important not to get caught up in the hype of people overstating their findings for personal gain.

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3. johnnyboy on June 10, 2011 8:21 AM writes...

Having collaborated a bit on post-MI regenerative cardiac studies in the past few years, I must say that I would put more hope on the approach of the research you cite (enhancing the endogenous regenerative response) than on stem cell regenerative therapy. If you're looking for hype with very few real results to back it up, stem cells are your field. To read the papers, you'd think stem cell therapy to cure infarcts is miraculous and just around the corner, where in reality it's still totally pie-in-the-sky (at least for post-MI - can't say about other applications, like neurological).

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4. Nick on June 13, 2011 7:17 AM writes...

Reminds me of the interest in gylcine antagonists and stroke recovery. If you had any rats that suffered a stroke, they were miracle cures. In humans, however, diddly squat. Lets hope these are more successful.

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5. rpg on June 13, 2011 10:30 AM writes...

I was at the press conference, and I've chatted with Paul Riley about his work.

It is totally out of order to suggest that the findings were overstated. It is a very exciting finding indeed, but what struck me about the statements from Nature magazine, from Riley himself and from Peter Weissberg (Medical Director of the BHF, which funds Riley's lab) is how understated everything was. They were crystal clear that it's not a miracle pill, that they don't know if it will translate to humans, that you'd have to give it to people at risk of an infarct, that we're ten years off even that kind of treatment &c.

The Business Insider article is wrong in its quoting of the BHF: Weissberg said that heart (self-)repair is the "holy grail of heart research", NOT this discovery! I can only imagine that the over-the-top coverage was written by journalists not at the briefing.

Oh, and the headline subs too.

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