December 27, 2007
Liver Fibrosis Stoppable In Mice

Lots of liver diseases kill by causing accumulation of scar tissue. Well, at least in mice the scarring process can be stopped and partially reversed with an inhibitor peptide.

University of California, San Diego researchers have proven in animal studies that fibrosis in the liver can be not only stopped, but reversed. Their discovery, to be published in PLoS Online on December 26, opens the door to treating and curing conditions that lead to excessive tissue scarring such as viral hepatitis, fatty liver disease, cirrhosis, pulmonary fibrosis, scleroderma and burns.

Six years ago, the UC San Diego School of Medicine research team discovered the cause of the excess fibrous tissue growth that leads to liver fibrosis and cirrhosis, and developed a way to block excess scar tissue in mice. At that time, the best hope seemed to be future development of a therapy that would prevent or stop damage in patients suffering from the excessive scarring related to liver or lung disease or severe burns.

In their current study, Martina Buck, Ph.D., assistant professor of medicine at UCSD and the Veterans Affairs San Diego Healthcare System, and Mario Chojkier, M.D., UCSD professor of medicine and liver specialist at the VA, show that by blocking a protein linked to overproduction of scar tissue, they can not only stop the progression of fibrosis in mice, but reverse some of the cell damage that already occurred.

We have been watching bioscience and biotechnological advances for many years. Isn't it about time this progress starts to translate into a whole bunch of disease cures? It is all well and good to watch the progress and marvel at the cleverness of the researchers who find ways to tease out the secrets of biological systems. But getting down to some curing treatments would be great. You might want to see cancer or heart disease cured first. But I'd be happy to see an end to death by liver cirrhosis as a starter.

Inhibition of a protein that actives growth of a type of cell involved in collagen production did the trick.

In response to liver injury – for example, cirrhosis caused by alcohol – hepatic stellate cell (HSC) activated by oxidative stress results in large amounts of collagen. Collagen is necessary to heal wounds, but excessive collagen causes scars in tissues. In this paper, the researchers showed that activation of a protein called RSK results in HSC activation and is critical for the progression of liver fibrosis. They theorized that the RSK pathway would be a potential therapeutic target, and developed an RSK inhibitory peptide to block activation of RSK.

The scientists used mice with severe liver fibrosis – similar to the condition in humans with cirrhosis of the liver – that was induced by chronic treatment with a liver toxin known to cause liver damage. The animals, which continued on the liver toxin, were given the RSK-inhibitory peptide. The peptide inhibited RSK activation, which stopped the HSC from proliferating. The peptide also directly activated the caspase or “executioner" protein, which killed the cells producing liver cirrhosis but not the normal cells.

“All control mice had severe liver fibrosis, while all mice that received the RSK-inhibitory peptide had minimal or no liver fibrosis,” said Buck.

Researchers probably had to spend many years teasing out the connection between the RSK protein, hepatic stellate cells, collagen production and scar tissue accumulation. But now they have something really powerful to show for it. Hurray.

But how many years will it take for a human treatment to make it to market?

Share |      Randall Parker, 2007 December 27 09:09 PM  Biotech Therapies


Comments
Alex Holt said at December 28, 2007 7:56 AM:

Well we can thank the FDA for the delay....

Fly said at December 28, 2007 2:50 PM:

"Well we can thank the FDA for the delay...."

Some of the delay is due to over zealous action by the FDA. However, in many cases the problem is that biology is complex.

Consider stem cell transplants after heart attacks. Since this is a surgical treatment rather than a drug treatment and because there is a long history of bone marrow transplants doctors have been fairly free to experiment. Even so progress has been slow. The biological knowledge and technology just hasn't been up to the task. You need to identify all the necessary stem cell types and their derived cell lines. You need cell markers and cell sorting technology. You need methods to culture and grow the cells. You need the right growth factors. You need to prepare the heart tissue so that the transplanted cells will survive and take up function. You need technology for monitoring the stem cells as they are incorporated into the tissue. This stuff takes time.

donald wilkins said at December 29, 2007 9:57 AM:

I believe both Alex and Fly are correct. However, I think we should allow patients who understand the risks to opt for experimental treatments.There are 17,000 people waiting for liver transplants; some might be helped with this technique.

I have heard two good arguments against this type of experimentation. First, the patient is not really making a decision baed on just the data. He will likely die until the current protocols. Why not throw the die and see what happens? This argument does not resonate with me. If I am going to die why not take a chance?

The second gives me more pause. If we start experimentation on humans too early with too little understanding of the biology, we might lose a number of subjects and the researchers would abandon a useful but immature technology. I would be willing to risk the experimenter's judgement rather than the FDA.

guy said at May 22, 2010 11:13 AM:

I know this is an ancient thread, but does anybody know the current status of this research? Liver is not going to last - tick-tock tick-tock.

thomas thorne said at July 3, 2011 9:41 PM:

Does anybody know the status of the research now? tick tock

thomas thorne said at July 7, 2011 5:35 PM:

This is an old article considering this is July 2011 but has anything been done to advance this work? The clock is ticking and I am interested in what ever information is out there.

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