Commercialization plenary summary: part 4 of 4
The last speaker of the commercialization plenary at the Till and McCulloch Meetings earlier this month was Dr. Stephen Minger from GE Healthcare, who shared GE’s perspective regarding the therapeutic and research potential of human stem cells. Previous to his role at GE Healthcare, Minger was the director of the Stem Cell Biology Lab at King’s College London, and his departure from academia to industry in 2009 was covered with intense interest from the academic community. Dr. Minger is also currently a director of the CCRM in Toronto.
Minger’s forte is growing human cells – large quantities of human cells – and his latest work through GE is in facilitating stem cell based small molecule screening to identify cardio and liver toxicity in earlier stages of clinical testing of drugs, which I discussed on this blog in early 2010.
Minger began by illustrating GE Healthcare’s worldwide commitment to research and development, spending about $1 billion annually. Minger’s Cell Technologies research group comprises about 300 people around the world that focus on technologies like automated stem cell extraction and high content drug screening.
“[GE Healthcare] made a major commitment to human embryonic stem (hES) cells for drug discovery”, explained Minger. “hES cells are the only reliable types of cells that can differentiate into useful cells for this purpose.”
According to Minger, one of the main reasons GE made such a large commitment to cell technologies was that management believed it would make a huge difference in how toxicology studies are done.
In recent years, many compounds have been withdrawn for cardiotoxicity, representing potential losses of huge investments in research and development. Minger cited eleven examples, including Grepafloxacin and Rofecoxib.
Industry collaboration in the field was presented as essential; a collaboration with Geron proved to be critical in advancing GE Healthcare’s toxicology work. “What we gained from Geron is the ability to grow large quantities of cells on an industrial scale. One of the first products that we created in collaboration with Geron was cardiomyocyte generation from h7 hES cells. It ended up being a 28 day process of selection with no genetic engineering.”
The cardiomyocytes Minger’s team produces can be frozen, thawed, and re-plated to reconstitute beating cardiac syncytia, which end up looking like cardiomyocytes based on common markers. “We end up verifying that 80% of these cells are ventricular and 18% atrial, which is very similar to the composition of a human heart.”
The audience also saw data showing the different sensitivities of human, canine, and rabbit cardiomyocytes to chemicals such as Terfenadine, which prevent cells from repolarizing and becoming ready for re-firing. The differences between human, rabbit and canine models show that the non-human models are 1-2 orders of magnitude less sensitive to action potential deviation by Terfenadine. “If we had relied on canine and rabbit models, we would only observe [Terfenadine] toxicity far out of the effective clinical range for humans.”
Minger then showed the results of several high content cardiotoxicity studies that made use of GE’s IN Cell Analyzer, an system capable of imaging full field 96 well plates in four colours in about 5-6 minutes. Using this technology, Minger’s team collaborated with counterparts in Genentech to identify cytotoxic anti-cancer compounds. The study managed to examine the dose-response effect of compounds on 19 cell parameters such as calcium transport, effects on mitochondria, and general viability affects, and were able to identify known cardiotoxicities of oncologic drugs.
As cell based medical technology becomes more patient specific, questions regarding whether conclusions in one genomic background can be generalized are also being raised. It’s known that drug sensitivity can very between individuals of different ethnic backgrounds, so research studies will need to consider more ethnic diversity by using hESC lines from all over the world explained Minger. “Researchers don’t usually get to see how a compound works across 100 different genomes until Phase 3 clinical trials. We can do that with this technology.”
At the end of the session, one audience member did ask Minger the inevitable question: Are you happy with your decision to “leave” academia?
His response was wholly positive. “The major reason I joined GE was to access thousands of scientists and technologists that make everything from consumer products to nuclear reactors. I’ve also found that the people at GE have very ethical standards. I’m having a lot of fun in my current job and can do much more being at GE.”