this finding. It takes a long time to develop a new field and call it your scientific home. So we were very interested in looking next at in vivo efficacy. And to do in vivo research on conditions like stroke requires specialist facilities. That year I moved from Berkeley to Ohio State University, where I have been ever since. So if you jump forward from 2000 to today, we are doing clinical trials today I never could have undertaken at my previous lab at Berkeley.
Focus: What was your first in vivo study?
Sen: I went to the di- rector of the clinical stroke program at Ohio State, Dr. Andrew Sliv- ka, PhD. Slivka had a laboratory where he studied stroke in rats that were spon- taneously hypertensive, and I asked him to test tocotrienols in his rats. We found that just by giving tocotrienols orally, not even by injection, we could de- crease stroke-induced injury to the brain in hypertensive rats. This was published in Stroke, journal of the American Heart As- sociation in 2005.2
The scientific response to our pa- per in Stroke was huge, and many people asked me if I thought it was only stroke, or also other forms of neurodegeneration? I still get asked that question today. And I have to say, I am sorry, but
I have dedicated my laboratory work to studying stroke. Other researchers are studying other forms of neurodegeneration, but in order for me to do my science well I need to take one disease all the way. And of course, people also said, there are hundreds of molecules that work in a mouse and a rat and don’t work in a human. It is widely understood that the brain of a rodent is small, and its geometry is quite differ- ent than a human brain, so if you want to show this might help hu-
trauma, and more like a car acci- dent than a naturally occurring stroke. And in another model, they’d take out the eyeball and go in and pinch the blood ves- sels in the brain. I also thought this was way too traumatic. I sat down with surgeons and neu- roradiologists and said, I need a cleaner, gentler approach. It took us several years to develop that approach, and our results of the first study using this model were published in 2008 in the Proceed- ings of the National Academy of Sciences.3
When we tested a model of stroke in dogs, we found that mixed tocotrienols showed a tremendous neuroprotective effect, even more so than in rodents.
mans, you need to go to a larger animal first. It was time for us to test tocotrienols in a larger ani- mal.
Focus: So you went to study dogs. But when you saw how stroke was routinely studied in dogs, you didn’t like it. You felt the dog and its brain were being traumatized. So what did you do?
Sen: I did not like the approach being used at that time to in- duced stroke in large animals. In one model they actually cut open the dog’s skull, then went in and physically pinched a blood ves- sel in the brain to create stroke. To me this was tremendous head
We demonstrated that we can go in with a dime size access route in the leg, and thread an endoscopy catheter all the way into the brain, into the mid-cerebral
artery where most stroke occurs, and simply create a reversible oc- clusion there. We then wake up the animal, and it’s very similar to a naturally occurring stroke. So we studied twenty dogs this way, and gave them tocotrienol-rich palm oil in a capsule (or place- bo) that had already been cleared as safe for human consumption. We tested the dogs’ brains by using MRI, and found a tremen- dous protective effect. In fact, we were able to demonstrate a far better effect in dogs than in rats.4 And at that point, as you might imagine, there was a floodgate of enthusiasm from scientists and sponsors. Even so, I still cannot
Focus April 2013 11
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