No announcement yet.

Drugs to Spur New Cells, and Without the Politics

  • Filter
  • Time
  • Show
Clear All
new posts

    Drugs to Spur New Cells, and Without the Politics

    Drugs to Spur New Cells, and Without the Politics


    RVINE, Calif. - As debate again heats up over cloning and stem cell research, several biotechnology companies are trying to develop a far less controversial approach to cell regeneration.

    The companies are actively working on drugs that stimulate the brain and other organs to grow new cells and repair themselves.

    Drugs do not face the same problems with rejection by a recipient's immune system that cells and tissues often do. And in most cases, giving drugs would not require the surgery that might be needed to implant new cells grown from stem cells.

    "It's certainly a lot easier to swallow a pill or take a spoonful of liquid than to have a hole drilled in your head and have embryonic stem cells put in," said Alvin J. Glasky, chief executive of NeoTherapeutics (news/quote), a small biotechnology company based here that is working on a berry-favored medicine to stimulate the brain to grow new cells.

    In addition, big pharmaceutical companies, which have been largely uninvolved in stem cell research, might be more interested in developing drugs to promote new cell growth. While cell therapies often require the use of a patient's own cells - a customized approach that is a departure for big drug companies - drugs that promote new cell growth could be mass-produced.

    "We can look forward to the time when any cell in the body can be regulated with natural factors to grow or be inhibited from growing," said William A. Haseltine, chief executive of Human Genome Sciences (news/quote). The company, based in Rockville, Md., is using a process of gene-hunting to find proteins that act as growth factors and is already testing in patients a protein that stimulates the healing of wounds.

    "That is the medicine that will be the new medicine for the next 20 years," he said. "Stem cells and their uses will be very limited because we don't know much about them."

    The drug approach to new cell growth has already produced some successes. The biotechnology industry's most lucrative drug, for example, is Amgen (news/quote)'s Epogen, which fights anemia through a human protein that stimulates the body to produce red blood cells. A protein developed by Curis Inc. (news/quote) of Cambridge, Mass., stimulates bone growth and is used as an alternative to a bone graft to treat fractures that do not heal.

    Still, using growth factors is not as easy as it sounds. Human Genome Sciences' wound-healing protein just failed to work in two clinical trials. And Regeneron Pharmaceuticals (news/quote) of Tarrytown, N.Y., has tested various nerve growth factors to treat illnesses like Lou Gehrig's disease and Parkinson's disease. The company's trials, some done in partnership with Amgen, have all failed. "We are experts in all this, and we've only been increasingly humbled by how difficult it is to create structure," said George D. Yancopoulos, Regeneron's chief scientific officer.

    The interest in stimulating the body to heal itself has been spurred by discoveries in recent years that organs like the brain and heart, which were thought not to have the ability to regenerate, appear to do so in certain circumstances. Various organs have been found to harbor small quantities of stem cells that can turn into specific types of cells to repair damage.

    But many scientists and biotechnology executives say they doubt that the drug strategy will work. The fact that people do not recover on their own from brain injuries or heart attacks probably indicates that the body cannot produce enough stem cells to make a difference.

    "Certainly being able to deliver the required number of cells directly from laboratory-isolated stem cells seems more straightforward technically," said Karl Johe, chief scientist at NeuralStem Biopharmaceuticals, a company working on cell therapies for brain disease.

    Some scientists say drugs will work better for some diseases, cells for others. Pancreatic cells are already restoring the ability of some diabetics to produce insulin.

    Growth factors can also stimulate the wrong cells, causing unintended effects. In Regeneron's tests, nerve growth factors in some cases made people sensitive to pain or changed their behavior, Dr. Yancopoulos said. Yet some of those unintended effects may help salvage Regeneron's business. One nerve growth factor, instead of alleviating a disease, made people feel full, and is now being tested as an obesity drug.

    Both Genentech (news/quote) and Chiron failed in clinical trials using growth factors to stimulate the body to grow new blood vessels and bypass clogged arteries.

    But despite the setbacks with growth factors, work is continuing. James H. Fallon, professor of anatomy and neurobiology at the University of California at Irvine, reported that a protein called transforming growth factor alpha stimulated the stem cells in the brains of rats to proliferate and migrate to the site of injuries similar to those caused by Parkinson's disease. The stem cells turned into neurons and repaired some of the damage. The work was partly sponsored by Stem Cell Pharmaceuticals, a private company in Seattle that wants to harness the growth factor as a drug.

    Dr. Piero Anversa and colleagues at New York Medical College in Valhalla, N.Y., used drugs to treat mice with heart attacks. The two drugs - stem cell factor and granulocyte colony stimulating factor - stimulated the bone marrow to produce numerous stem cells, which entered the bloodstream, migrated to the damaged heart, and turned into new heart muscle. Only 4 of 27 mice given the drugs died from their heart attacks, compared with 43 of 52 that had not been given the drugs.

    In some cases, drugs will not be any easier for patients than cell implants. The brain, for instance, is protected by a barrier that keeps out large proteins, so growth factors must be injected directly into the brain, just as for a cell implant.

    Several companies are trying to develop so-called small-molecule drugs that can be taken orally and can pass through the blood brain barrier, but this has not proved easy. Amgen and Guilford Pharmaceuticals (news/quote) announced in July that such a drug was not effective in a clinical trial in treating Parkinson's disease.

    NeoTherapeutics now seems to be the front-runner in the oral drug approach. Its drug, Neotrofin, appears to be able to stimulate the production of certain nerve growth factors and stem cells in animals. The drug is being tested on Alzheimer's disease patients in a late-stage clinical trial and, if all goes well, it could reach the market by 2004. NeoTherapeutics has also begun testing the drug on patients with Parkinson's disease and spinal cord injuries.

    Many investors and other scientists are skeptical, saying that Dr. Glasky has a reputation for making premature claims of success. For instance, he said in an interview that Neotrofin might work for every neurological disease, potentially becoming the biggest-selling drug ever.

    Neotrofin failed in the first big clinical trial, though the company says it now realizes it used too small a dose. Its shares closed yesterday at $3.80, down from a high around $24 early in 2000.

    "It's like the boy who cried wolf," said Harry M. Tracy, publisher of NeuroInvestment, a newsletter that follows companies developing treatments for neurological diseases. "People are very wary of taking him seriously." Still, he thinks there is a chance that the company will succeed. Results of the Alzheimer's clinical trial are expected early next year. Whether the drug works or not, he said, "they are going to know that a whole lot sooner than they'll know that about embryonic stem cells


    So claims about netrfine is exagerated and premature?

    I would like to know your frank opinion about Neotheraphitics...



      any comments?


        Max, in previous postings, I have indicated that I think that concept of using drugs to stimulate the body's own stem cells is a wonderful idea.

        At the Society for Neuroscience, there was a poster from the company that showed the data. There was about a 20% increase in the number of BRDU-labelled (these are cells that are dividing and thus may be stem cells) in some parts of the brain and spinal cord.

        Mark Tuszynski's lab also showed that AIT-082 significantly increased neurotrophin levels in the brain of rats when they were fed the drug in their drinking water.

        I anxiously await the results of the current trial of AIT-082 in subacute spinal cord injury.



          Max, I want to comment a little bit more about the situation with Neotherapeutics. Most smart companies today engage in what is called "expectation management". When your company's future (and stock prices) depends on public perception of the success or failure of your clinical trials, you have to be very careful what you say.

          Clinical trials are risky. There are so many reasons for a trial to fail and most companies at most have 1-2 chances to make it. Investors will abandon you if you have two failures in a row. So, the crux of the game is to lower expectations so that even if your trial is not as successful as you hope, it will not be regarded as a failure. Of course, if your trial results are much better than you predicted publicly, your stock will bound.

          Unfortunately, Neotherapeutics made AIT-082 seem like a miracle grow drug. Based on a 20% increase in BRDU labelling, some evidence suggesting increased brain neurotrophin, and some preliminary clinical trial data, they came out like a charging bull. It takes discipline to rein in the tongue and not let the hope splash out in such a situation.

          It is not unlike predicting that your company will earn $100 million profit and you make only $50 million. While $50 million is nothing to sneeze at and may be a lot more than your company has ever made, people will still regard your company as having failed.

          The same is true for scientists in general when they talk about their results. Too many scientists make big claims but fail to follow through with big results that match the raised expectations. The most successful laboratories understate the claims and let the results speak for themselves.

          Ultimately, we in the community must learn to see through the gamesmanship and get to the truth. We must learn to be skeptical of unsubstantiated claims of landfall but also not jump off the boat the moment the seas get rough.



            Thanx Wise,

            for clearing this matter