Kevin Eggan0:00
Thanks Mark and hello to all of you. I'd like to introduce you to an even further concept: the idea that we could use stem cell biology and reprogramming technologies to access classes of human cells that we've never been able to study in the laboratory, let alone use for therapeutic discovery. This is an idea which I think really maximizes some of the unique properties of pluripotent stem cells like human embryonic stem cells, as we can make a limitless supply of these cells for the first time.
The crucible in which we've been trying to employ this strategy is a devastating neurological condition called amyotrophic lateral sclerosis, which many of you may know as Lou Gehrig's disease. This is a progressive and almost universally fatal neurological condition characterized by the destruction of the nerve cells which connect your brain to your musculature and that you use for every voluntary movement. There's only one drug on the market for this condition, which has a small statistical effect on lifespan, marketed by Sanofi. There are no disease-altering or curative therapeutics for ALS. I would submit to you this is because we know very little about the particular human cells that degenerate in this condition and haven't been able to study them before.
The classical approach for studying this disease has been to learn about the genetics which underlie this condition and then make mouse models which overexpress the mutant forms that make patients sick. So far, there have been hundreds of clinical trials which have come forward from therapeutics developed through that approach. There's been a 100 percent correlation between success in those animal models and failure in clinical trials. So clearly we need a new strategy. The idea that we might be able to mimic things that we have found in patients and apply them in the tissue culture dish through this sort of strategy is becoming more and more attractive. I'm here today to say that we've had some of our first fledgling successes in that kind of activity.
Clinical neurologists have discovered now that there are very early electrical changes in the brains of ALS patients which even begin before they become outwardly sick. One of the questions that we've been asking is whether or not we can model aspects of these electrophysiological changes actually in the tissue culture dish with a patient's own motor neurons. The strategy that we take for doing that is to take easily obtained cells from patients like skin or blood and through reprogramming and stem cell technologies, turn them into the types of cells that are actually degenerating in that patient.
Through collaborations with many people throughout the Harvard System, including neurologists at MGH, physiologists in Clifford Woolf's lab at Children's Hospital, and my colleague Adam Cohen in the Chemistry Department here at Harvard, we've been able to show that indeed the cells of those patients in the dish manifest some aspects of those same changes that you see within their brain. We've been able to use those to identify potential therapeutics which we hope might modify those electrophysiological changes in the patient's own brain. Excitingly, we now are beginning to get some of the first clinical returns on those experiments.
The key discovery that we made implicated an already approved anti-epileptic drug as potentially being disease modifying in ALS. We actually were able to take that drug into the clinic. It's a GSK compound. GSK also has taken that compound into healthy patients in a shorter trial. What I can say is that the disease-in-a-dish model that we used, at least so far in this first control study, had exactly the effect that we predicted that it would within those control individuals. We're now waiting over the course of this next year for what the clinical readout will look like in ALS. So I can't say for sure yet whether or not this will actually have a disease-modifying effect in patients, but at least we know the disease-in-a-dish predicted what the chemical effects would be in healthy populations, and now we're waiting to see.
I think there are some real obvious commercial possibilities that would come from this. Three years ago, along with Adam in the Chemistry Department, we co-founded a company, Q-State Biosciences, which now has real collaborations using these types of technology in pain, epilepsy, cardio, and cardio discovery. I think that there are opportunities looking out into the future for using these types of technologies both for very disease-oriented company generation as well as for approaches to make new forms of diagnostics that would go beyond DNA sequencing for predicting functional changes in patients. Thank you very much.
