By Rob Stein, The Washington Post
Embryonic stem cells have numerous pitfalls in addition to the ethical dilemmas. While the concept of a “blank slate” cell is extremely attractive in terms of generating new tissues for transplantation and organ replacement, the problem is that these cells are so young that they do not properly “know” how to integrate with existing tissues. This causes the problem of possible dysfunction of the cellular products made from the cells, but also causes the issue of cancer formation. Many studies have demonstrated that administration of embryonic stem cells, or products made from them form cancers when injected into mice that lack an immune system.
Because of the risks associated with embryonic stem cells, the FDA has been historically reluctant to allow initiation of clinical trials with them. The leader of the field of embryonic stem cells is Geron, the company that funded the research that lead to the discovery of human embryonic stem cells, as well as the company that has the exclusive license for their commercial use. The business of embryonic stem cells is associated with large financial investments. Specifically, patents are not only associated with the cells themselves but one methods of growing the cells and methods of selecting the cells to reduce the possibility of cancer formation. In some ways people believe that embryonic stem cells are an exercise in science because adult stem cells have been demonstrated to elicit numerous therapeutic effects without the risks.
Last year a monumental study was initiated in that the FDA allowed for the first human use of an embryonic stem cell product. The company Geron was granted approval to treat patients with spinal cord injury using embryonic stem cell derived oligodendrocytes, the cells that generate the myelin that lines the nerves.
Today, information was released on the first patient that was treated with these cells. The patient was a partially paralyzed young man, Timothy J. Atchison, 21, known to family and friends as T.J.
T.J. was a student at the University of Alabama College of Nursing when he was partially paralyzed in a Sept. 25 car accident, his aunt and father said. He agreed to let doctors infuse more than 2 million cells made from stem cells into his spine 13 days later at the Shepherd Center in Atlanta, according to his aunt and a family friend.
While the primary endpoint of the trial is to demonstrate safety, doctors are also testing whether the cells restore sensation and movement. It was too soon to tell whether the cells were helping T.J., Angela Atchison said. “They said it would be about a year before they’ll know if there’s any difference — if it takes,” she said. “We’re just hoping and praying that it works.”
T.J.’s father, Timothy Atchison of Millry, said his son had maintained a positive attitude, beginning when he was in the emergency room after the accident. and understood how seriously he was injured.
“He said, whatever the Lord leaves him with, he’ll do the best he can with it,” the father said in a phone interview Monday. He would not directly acknowledge that his son was in the stem cell study, but confirmed details including his Shepherd Center treatment. “I’ll put it this way, they tested a lot of folks, and only one made the cut,” he said during another interview Tuesday. “You can read between the lines.”
First patient to get stem cell therapy identified
Adult Stem Cell Clinical Trials Showing Success
A Number of Clinical Trials Using Adult Stem Cells Are Showing Early Success
Dozens of adult stem cell treatments are moving through clinical trials and showing early success, raising hopes that some could reach the market within five years. ‘It will only take a few successes to really change the field,’ said Gil Van Bokkelen, chief executive of Athersys and chairman of the Alliance for Regenerative Medicine. ‘As you see things getting closer and closer to that tipping point, you’re going to see a frenzy of activity take place.’ Many of the trials focus on heart disease and inflammatory conditions, some of the biggest markets in medicine. The cells used are derived from adult tissue such as fat, or bone marrow, thereby circumventing the ethical concerns raised by the use of cells derived from embryos.
Data for the most part remains early, but as more results emerge, pharmaceutical companies are beginning to take note. ‘A lot of big companies are looking to place bets on some Phase II products once that data has been confirmed,’ said Paul Schmitt, managing partner at Novitas Capital. ‘Even now they’re attending all the medical meetings and talking to all the stem cell companies.’ Steven Martin, from Aspire Capital Partners LLC said they were willing to be patients as the benefits from treatment could be enormous. ‘My philosophy in the stem cell space is that it’s very difficult at this point to pick the winners and losers,’ he said. ‘We believe that over time there will be some very significant clinical progress, and valuations will improve, but we’re still a long way from an approved therapy.’
Aastrom Biosciences recently presented promising results from a mid-stage trial of its treatment for patients with critical limb ischemia, a disease in which blood flow to the extremities is restricted, at the American Heart Association’s annual meeting. A mid-stage trial from Australia’s Mesoblast Ltd showed its stem cell product reduced the rate of heart attacks and the need for artery clearing procedures by 78 per cent. ‘We’re actually developing products now,’ said Timothy Mayleben, chief executive of Aastrom, which is using cells derived from a patient’s own bone marrow to develop treatments for cardiovascular disease. ‘For the first time you are starting to see data being presented at major medical meetings.’ Pfizer Inc, Johnson & Johnson and Roche Holding AG are members of the Alliance for Regenerative Medicine, a nonprofit group that promotes awareness of the field. Pfizer has a regenerative medicine unit and a partnership with Athersys. But their projects are small as they want to wait to see data in hundreds of patients. The promise of stem cells, which have been used for 40 years in bone marrow transplants, lies in their ability to repair tissue, reduce inflammation, regulate the immune system, and respond to calls for help from multiple places inside the body. Stem cells are the body’s master cells – blank slates that renew themselves and mature into specific cell types in the heart, muscle and other organs.
Embryonic stem cells are uniquely capable of differentiating into every type of mature cell in the body, and were long viewed as the most promising for regenerating tissue. But harvesting stem cells from embryos requires the destruction of the embryo itself, a process opposed by conservative Christian groups. Moreover, their endless capacity to divide can lead to the formation of teratomas, or stem cell cancers. Recently, Geron Corp, the world’s leading embryonic stem cell company, said it could no longer fund its stem cell work and would focus on developing cancer drugs. It closed its trial for spinal cord injury. Unlike embryonic stem cells, adult stem cells have a more limited capacity to differentiate, but appear able to reduce inflammation and promote blood vessel formation. Furthermore, they can respond to damage in the body in a flexible and dynamic way, offering advantages over traditional drugs.
‘They seem to be preprogrammed to act some way in tissue repair, not to form an organ or a tissue,’ said Douglas Losordo, head of stem cell research at Baxter International Inc, which is developing cell therapies for heart disease. ‘The cells that we use are very effective at stimulating the formation of new blood vessels, but if I wanted to make a brain cell out of those cells they would not be very good at it.’ These are the type of stem cell treatments, delivered by infusion, injection or catheter, that are being developed today.
‘We wanted to create a product that everyone could receive and not have to match every donor to every recipient,’ said Robert Hariri, chief executive of Celgene’s Cellular Therapeutics unit.
Different types of stem cell are being used for different diseases. Cytori Therapeutics is developing a heart disease product derived from fat cells, for example, while Celgene is using placental cells for Crohn’s disease and rheumatoid arthritis therapies. Fetal cells are also being explored. Neuralstem Inc, for example, is developing treatments for neurological disorders from an aborted fetus. As cell therapies move further through clinical trials, companies will need more money, and funding is scarce.
Yet even if companies remain afloat long enough to bring a product through late-stage clinical trials, it is unclear what regulators like the Food and Drug Administration will require in order to approve them Some believe the regulatory hurdles for treatments derived from a patient’s own cells will be lower than those where the cells come from donors, since there is less risk of cell rejection. However, no clear pathway has yet been established. ‘We need a clear, consistent and rigorous regulatory framework,’ said Athersys’s Van Bokkelen. ‘The FDA is actually willing to provide lots of guidance and assistance to sponsors, if you just ask them.’
