Wednesday, June 22, 2011
Drug Makes Hearts Repair Themselves
The neat trick here is to restore activity in dormant cells already in the heart. It is presently no particular help for someone who has had a heart attack, though that obviously could change as more work is done, but it is just as obviously indicated for a patient that has suffered one heart attack.
Many of the patients suffering from heart failure are in fact suffering from the damage inflicted by even several attacks. If one can minimize the effects of the first such attack, then been able to reverse the effects of late attacks is a clear winner.
In the past month we have also seen additional therapy for heart failure emerge from the labs. As stated this was considered untreatable. We are now opening the floodgates to major improvements on the outlook for heart failure. Millions presently are so diagnosed and reversing this problem is a huge boon.
Drug makes hearts repair themselves
By James GallagherHealth reporter, BBC News
More people are surviving heart attacks, but that means more are living with heart failure
The damage caused by a heart attack had previously been considered permanent.
But a study in the journal Nature showed the drug, thymosin beta 4, if used in advance of a heart attack, was able to "prime" the heart for repair.
The British Heart Foundation described repair as the "holy grail of heart research", but said any treatment in humans was years away.
Due to advances in health care the number of people dying from coronary heart disease is falling.
But those living with heart failure are on the rise - more than 750,000 people have the condition in the
The researchers at
looked at a group of cells which are able to transform into different types of
heart tissue in an embryo. London
Deaths from coronary heart disease
1961 - 165,216
2001 - 117,743
2009 - 80,223
Estimated people living with heart failure
1961 - 100,000
1971 - 300,000
2010 - 750,000
Source: British Heart Foundation
In adults epicardium-derived progenitor cells line the heart, but have become dormant.
Scientists used a chemical, thymosin beta 4, to "wake them up".
Professor Paul Riley, from the
College , said: "The adult epicardial
cells which line the muscle of the heart can be activated, move inward and give
rise to new heart muscle." London
"We saw an improvement in the ejection fraction, in the ability of the heart to pump out blood, of 25%."
As well as pumping more blood, the scar tissue was reduced and the walls of the heart became thicker.
Peter Weissberg, medical director of the British Heart Foundation, said he was "very excited" about the research but warned the scale of improvement seen in animals was rarely seen in humans.
Epicardium derived progenitor cells (in red) lining the heart
However, he argued that even a small improvement would have a dramatic impact on people's quality of life.
"A normal heart has lots of spare capacity. In patients with heart failure it is working flat out just to sit down [and] it's like running a marathon," he said.
"You could turn a patient from somebody who's gasping while sitting in a chair to somebody who can sit comfortably in a chair."
The mice needed to take the drug in advance of a heart attack in order for it to be effective. As the researchers put it, "the priming effect is key".
If a similar drug could be found to be effective in humans, then the researchers believe it would need to be prescribed in a similar way to statins.
Professor Riley said "I could envisage a patient known to be at risk of a heart attack - either because of family history or warning signs spotted by their GP - taking an oral tablet, which would prime their heart so that if they had a heart attack the damage could be repaired."
He said this could be available in 10 years.
The British Heart Foundation, which funded the study, said repairing a damaged heart was the "holy grail" of heart research.
The results strengthened the evidence that drugs could be used to prevent the onset of heart failure, it said.
De novo cardiomyocytes from within the activated adult heart after injury
Nicola Smart, Sveva Bollini, Karina N. Dubé, Joaquim M. Vieira, Bin Zhou, Sean Davidson, Derek Yellon, Johannes Riegler, Anthony N. Price, Mark F. Lythgoe, William T. Pu & Paul R. Riley
Nature Received 16 March 2010, Accepted 13 May 2011, Published online 08 June 2011
A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction1. A therapeutic ideal—relative to cell transplantation—would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm’s tumour 1 (Wt1), through priming by thymosin β4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells2 with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards resident-cell-based therapy in human ischaemic heart disease.