Madison, Wis. – As Wisconsin observed the 10-year anniversary of James Thomson’s embryonic stem (ES) cell discovery, some wonder whether the ensuing controversy over the destruction of human embryos has been worthwhile. In those 10 years, no therapies have come from the discovery, so were opponents correct that this research was not only unethical, but also irrelevant?
While there have been no headline-grabbing ES-based therapies, the technology is surely changing the way that medicine is practiced. This was illustrated by recent events in Madison, including the World Stem Cell Summit in September and a more recent celebration of the ten-year anniversary of Thomson’s discovery put on by the Wisconsin Academy of Arts and Sciences.
The anniversary event featured keynote talks by Thomson, the University of Wisconsin-Madison professor cellular biologist, and Michael West, CEO of BioTime, Inc. and founder of Geron, a West Coast stem cell company.
Thomson sounded his usual cautionary note, saying it will be very difficult to use ES cells to directly treat disease. But he also said that even if they never make it into the clinic, ES cells would profoundly affect the future of medicine because they provide laboratory access to human tissues that had been inaccessible before. This allows scientists to see what goes wrong with the specific cell types that cause Parkinson’s and cardiovascular diseases, diabetes, and other maladies. This, Thomson said, will lead to the development of new drugs and therapies to treat and prevent such diseases.
Thomson also explained that the different cell types that can be derived from ES cells enable researchers to directly test new drugs on different human tissues. He suggested that this will both dramatically reduce the number of animals used in drug and toxicity testing and allow more precise assessment of new drug efficacy and toxicity.
This was put into perspective at the Stem Cell Summit by John McNeish, head of Pfizer’s regenerative medicine efforts. He said that 10 to 16 percent of all new drugs fail during Phase I clinical trials alone due to cardiotoxicity. Many more drugs fail due to liver, kidney, and other organ-specific toxicities.
Overall, about 92 percent of new drugs that enter clinical trials fail due to lack of efficacy or to toxicity, according to the Food and Drug Administration. This means that potential drug toxicity is inefficiently measured in current animal models, making drug makers gamble early on that their new drugs won’t show organ-specific toxicity – a gamble they lose nine times out of 10.
ES cell technology therefore promises to provide tissues on which to test and eliminate potentially toxic drugs much earlier in the development pipeline, potentially saving billions in drug development costs, according to the FDA.
ES cell-derived research tools enter the marketplace
Thomson and others from UW-Madison founded Cellular Dynamics International to grow different tissues from ES cells. According to Tim Kamp, a UW-Madison cardiologist and CDI co-founder, the company now sells heart cells to Roche and Covance for drug testing purposes. CDI grows the heart cells in-house and then sells them as research tools. Thus, they retain control of the ES cells and the developmental process, while providing a renewable stream of cellular tools that researchers can purchase.
At this time, CDI only markets heart cells, Kamp said. But, according to Chris Kendrick-Parker, CDI’s chief commercial officer, the company either has agreements with or is talking to the “all of the top 20 pharma companies” to provide cells for toxicity testing.
Besides CDI, Geron, and San Francisco’s VistaGen Therapeutics also use ES cells to produce cells from the heart, pancreas, liver, and other organs for similar purposes. The European company Cellartis provides AstraZeneca with ESC-derived liver cells for toxicity testing, but only at very low numbers that are not useful for high-throughput-screening of new drugs. Cellartis also provides Pfizer with embryonic cells to test for birth defects.
Clearly, ES cells as drug testing and research tools is a growing international market. At the Stem Cell Summit, Pfizer stem cell expert John Hambor said this market currently stands at $1.5 billion and is predicted to grow 20 percent annually in the foreseeable future.
Clinical trials on the horizon?
Michael West is more optimistic than Thomson that ES cell-based therapies soon will happen. He cited the very high interest in the technology shown by several biotech and pharmaceutical companies as the driving force that soon will propel ES cells into the clinic.
Some biotechs already are pushing hard to begin clinical trials of ES cell-based therapies. For instance, last spring Geron submitted an Investigational New Drug (IND) application to the FDA for permission to undertake the first ES cell clinical trial to treat spinal cord injuries. According to the company, the trial had been in the works for four years, but the FDA issued a clinical hold because they have not yet established safety and efficacy guidelines for ES cell-based therapies. According to an article last May in the science journal Nature, there also is speculation that President Bush’s objection to ES cell research helped force the FDA to put the trial on hold.
Geron also is planning ES cell clinical trials for heart disease, while Advanced Cell Technology in Los Angeles is poised to submit an IND to use these cells to treat macular degeneration. San Diego’s Novocell, with funding from Johnson & Johnson, is preparing for ES cell clinical trials to treat diabetes.
After 10 years…
So, 10 years after Thomson’s discovery, ES cells are just now entering the market as research tools for drug and toxicity testing and clinical trials loom on the horizon. At this point, the holdup is so the FDA can figure out how to monitor the trials.
Furthermore, with the Obama administration, political constraints on the FDA to approve ES cell-based trials will likely be removed next year.