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Converting existing heart cells into a biological pacemaker

cardiac heart biotech medicine rehabilitation

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#1 Orpheus

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Posted 17 December 2012 - 11:47 PM

This was a real "why didn't I think of this?" moment for me.

Normal heart muscle cells (cardiomyocytes) are design to contract and propagate the activating signal to trigger their neighbors, some of them (the Purkinje system) are slightly modified to transmit the signal somewhat better/faster to assure a coordinated contraction. A few select bundles are designed to 'leak' ions and trigger themselves at a constant rate. The Sino-Atrial Node (SAN) is the primary pacemaker for the entire heart. A second bundle, the Atrio-Ventricular Node (AVN) located between the atria (receiving chambers) and ventricles (pumping chambers) of the heart can act as a backup.

All of these cells are nearly identical. It's just a matter of a few different genes being activated -- and now some clever scientists have isolated the gene and implanted it into normal heart cells to convert them into pacemaker cells. I've known this since I was a kid, but I missed the Big Idea.

It wasn't easy. Ten years of work went into isolating one key gene that would, by itself, enable the pacemaker function without (thus far) any known side effects. And it's just an animal study thus far, so we can't really be sure this will be a game changer that could almost eliminate electrical pacemaker implants, but it looks very promising.

The gene could be implanted in a simple existing procedure: threading a catheter from an incision in the thigh to a desired point in the heart and injecting a tiny amount of [non-replicating] gene transducing "virus". In the animal experiments, it took just days for a cluster of heart cells to convert.

Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18 Nature Biotechnology, published online Dec 16, 2012 doi:10.1038/nbt.2465

#2 RJDiogenes

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Posted 18 December 2012 - 07:35 PM

Simply amazing.  I wonder if this is permanent, or if new cells will need to be converted periodically.  In either case, it's a wonderful development.  This ability to control the expression of genes by transducing viruses is the real game changer-- how long before our entire biology becomes customizable and we become essentially immortal?
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#3 Orpheus

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Posted 18 December 2012 - 10:26 PM

Though I can think of some cellular transformation mechanisms that don't affect alter chromosomal DNA and would therefore not necessarily be passed on after a cell division, the transformation would almost certainly be permanent in the transformed cells, and is extremely likely to be passed on after cell division, so I'd bet that a single treatment would usually be a "permanent cure".

I put that in quotes because ongoing damage could require a re-treatment in some cases, but the first treatment wouldn't 'wear off'.

#4 RJDiogenes

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Posted 19 December 2012 - 07:54 PM

So it's actually hereditable on a cellular level.  That's fantastic. I wonder how long before it goes to Human trials.
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#5 Orpheus

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Posted 20 December 2012 - 12:22 AM

No, not heritable (that would mean it passed to your offspring). It is passed to the descendants of the treated cells (other heart cells), but all those die when you do. It doesn't get into your zygotes (eggs and sperm)

I think you understood, but I had to clarify because some forms of gene therapy COULD potentially be heritable.

That's actually something we're wary of. Remember the Asgard!

#6 RJDiogenes

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Posted 20 December 2012 - 07:16 PM

Yeah, that's why I said on a cellular level.  Maybe it's the wrong word.

Perhaps the Asgard were doomed by a misnomer.  :(
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#7 Orpheus

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Posted 20 December 2012 - 10:27 PM

I've always feared I'd die of a regrettable spoonerism, myself

#8 RJDiogenes

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Posted 21 December 2012 - 07:58 PM

I don't fork around with Spoonerism.  I'm more of a pun guy.
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