As we reach the ten year anniversary of UW-Madison Professor, Jamie Thomson’s, discovery of how to grow human embryonic stem cells (ESCs), one wonders whether this has been worth the controversy that ensued over the destruction of human embryos in order to obtain the stem cells. After all, 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 ESC-based therapies, the technology is surely changing the way that medicine will be done. This was illustrated by recent events in Madison, including the World Stem Cell Summit held last 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 and Michael West, CEO of BioTime, Inc., and founder of Geron, a West Coast stem cell company.
Thomson sounded his usual cautionary note, saying that it will be very difficult to use ESCs to directly treat disease. But, he also said that even if they never make it into the clinic; ESCs will profoundly affect the future of medicine. ESCs give us laboratory access to human tissues that we had not been able to get at before. This lets scientists 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 ESCs enables 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 10-16% 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% of new drugs that enter clinical trials fail due to lack of efficacy or to toxicity, according to the FDA’s web site. 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 that they lose nine times out of ten. ESC 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.
ESC-derived research tools are entering the marketplace
Thomson and others from the UW-Madison, recently founded Cellular Dynamics International, or CDI, to grow different tissues from ESCs. 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 ESCs and the developmental process, while providing a renewable stream of cellular tools that researchers can purchase. At this time, CDI only markets heart cells, said Kamp. But, according to Chris Kendrick-Parker, CDI Chief Commercial Officer, the company has agreements with, or is talking to the “all of the top 20 pharma companies” to provide cells for toxicity testing.
Besides CDI, the Menlo Park biotech company, Geron Corp., and San Francisco’s Vistagen Therapeutics also use ESCs 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, ESCs as drug testing and research tools is a growing international market, which Pfizer stem cell expert, John Hambor, said at the Stem Cell Summit, currently stands at $1.5 billion and is predicted to grow 20% annually in the foreseeable future.
Clinical trials on the horizon?
Michael West is more optimistic than Thomson that ESC-based therapies will soon 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 ESCs into the clinic.
Some biotechs already are pushing hard to begin clinical trials of ESC-based therapies. For instance, last Spring, Geron submitted an Investigational New Drug application (IND) to the FDA for permission to undertake the first ESC clinical trial to treat spinal cord injuries. According to a company press release, the trial had been in the works for four years, but the FDA issued a Clinical Hold because they have not yet established ensure safety and efficacy guidelines for ESC-based therapies. According to an article last May in the science journal, Nature, there also is speculation that President Bush’s objection to ESC research helped force the FDA to put the trial on hold.
Geron also is planning ESC clinical trials for heart disease, while Advanced Cell Technology in Los Angeles has indicated that it is close to submitting an IND to use ESCs to treat macular degeneration. San Diego’s Novocell, with funding from Johnson & Johnson, is preparing for ESC clinical trials to treat diabetes.
So, ten years after Thomson’s discovery, ESCs 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 ESC-based trials will likely be removed next year.
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