Turning Stem Cell Biology into Stem Cell Medicine
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Turning Stem Cell Biology into Stem Cell Medicine


They asked me to talk with you about what
floats my boat. What gets me to do what I do. I’m going to start by telling you why
all I want to do is stay in bed with covers over my head. Let me tell you about the typical
life of a university scientist. Everything that happens in our lab we’re responsible
for. Not just the ideas but raising the money. Every technician, every student, every post
doc, our own salaries, we have to raise it. That’s a lot to carry on our backs. We’re
pretty much on our own and in the best of times the National Institutes of Health sends
back four out of every five grant applications that it receives unfunded. Now, amazingly
enough we can live with that. Actually, we consider that the good times cause right now
they turned down nine out of ten or worse. In fact I have a colleague who sent an application
to one of the major charities in the United States. She got a phone call to tell her that
her grant scored number one out of one hundred sixty four applications and they weren’t sure
that they had the money to fund it. This is the only developing country in the world that
is not raising its science budgets where people who do what I do are fighting for their very
survival. There are laboratories across this country that our closing down. Our brightest
young people look at this and ask themselves why would they want to do this and on top
of this we have the shutdown. For Science, this means the National Institutes of Health
is closed. The National Science Foundation is closed. The grant giving bodies of the
Department of Defense are closed. No grants are being submitted. The review sessions to
evaluate grants are cancelled and these sessions require bringing together twenty or thirty
busy people to review these grants. So getting them going again is going to be very difficult
on top of all the human tragedies that are caused by the shutdown. So why do I do this?
Well, let’s start with our cancer work. Now, let’s turn the slides on if we could. We work
on a lot of horrible diseases, top of the list is cancer and one of the cancers we work
on is one of the most deadly of all, malignant brain tumors. These are cancers that kill
people usually within six to nine months or so, progress in treating them has been very
poor and we discovered new molecular pathways that enable this work to go forward more quickly
that look really promising. But, we don’t have the time it is going to take, the fifteen
to twenty years, to develop these drugs and more importantly, the people with these diseases
don’t have the time for normal approaches. So, I’ve committed us to a different approach.
Approach that I call the shot on go program to shorten the path to the clinic and in this
program what we do is we develop new applications of known properties of existing drugs and
we discover new properties of existing drugs. Why? Because we all ready know they work in
humans, the toxicology’s done, the dosing and the pharmoco kinetics are all done which
means that the number of years that it takes to get into a clinical trial is shorten enormously.
The traditional approach it might take ten or fifteen years from discovery to go to a
clinical trial with a shot on go program it may be one or two years. I’ll show you one
example. That picture of survival times in mice whose brains have been implanted with
human glial blastoma cells, the most malignant of brain tumors. We let the tumors grow for
three or four weeks and then we start treatment. The black line shows you mice that are only
treated with saline solution. The red line shows you mice that are treated with the front
line treatment for glial blastoma which doesn’t provide any benefit to these animals plus
one of the drugs that we discovered and you can see that the tumor growth is suppressed
for two weeks of treatment and when we stopped treatment instead of the tumors re-growing
,they shrank and they shrank and they continued shrinking. And the first tumors don’t come
back until a hundred days after treatment. One of the mice in this pilot experiment we
didn’t even see a tumor six months after treatment. We finally sacrificed the mouse to see what
was going on. This is a pilot experiment. This is a drug that’s already proved, even
better than that, it is a generic drug. We don’t have to negotiate with any pharmaceutical
companies. We can just go forward with this. This work is approached in a way that is unique
to Rochester. Our colleagues Hartman Land and Helene McMurray, at the medical school,
like us, have discovered pathways that nobody else works on that appear to be essential
for many many types of cancers and the pathways they work on, the pathways that we work on
both seem a minimal to these shot on goal approaches. We work with Dr. John Elfor, in
the Department of Orthopedics, on developing new ways of treating peripheral nerve injuries,
traumatic nerve injuries, gunshot wounds, crushed injuries, that again look like we’re
able to greatly hasten the time of recovery. We work on some awful genetic diseases, particularly
interested in a type of disease called lysosomal storage disorder. A lysosom is a part of your
cell that’s involved in breaking down proteins and lipids to provide nutrients for the cell.
Lot of people have mutations in enzymes that are necessary for these to work. If you only
have one mutation, you’re fine. But sometimes, someone marries someone who he has a mutation
in the same enzyme and some of the kids inherit two mutated genes and their lives can be short
and miserable. Very sick at birth, death within two years. None of them have anything like
the quality of life that we would like for our children. We approach this too with the
shot on go program and I am going to show you three ten second movies. That black blob
at the top is a mouse and if you can start at movie running you’ll see that mouse running
around, I hope, there he goes and showing mouse normal behavior. In the next slide,
we’re going to show you a mouse that has one of these diseases and it is so this mouse
is twenty five days old, it has about another two weeks to live. What I want you to pay
attention to is that it doesn’t move much. It’s when it moves, it shivers, it’s weight
support is very poor. So, start the program. Start the movie. And there he is, poor, sick
little guy. Not not a good quality of life, not going to be a long life. So Christopher
Falson, Nicolle Scott, two of my graduate students, have discovered pathways, novel
pathways involved in causing this damage. We have discovered drugs that prevent this
damage and this is one of our pilot experiments of a mouse treated with our first drug. So,
Let’s start that one. And, this guy looks pretty good, looks pretty normal. This is
also a drug that’s already approved for human use. In this work we’ve also discovered a
lot of bad drugs. We’ve discovered drugs that look like they might make these diseases worse
and some of these drugs are already used to treat these kids so that’s a real concern.
But, we have also opened up the door to a problem of tremendous interest. If you carry
a mutation, one mutation for these diseases, you might think you’re normal, but we know
that for example, that one of these diseases call gashay disease, you have a six fold increased
risk of developing Parkinson’s disease. It is the strongest genetic risk factor for Parkinson’s
disease. Why? Well, what we’re testing now is the idea that its exposure to these bad
drugs. And I can tell by looking at you that there’s quite a few of you in here who are
taking some of the drugs that are on our bad hit list just by your age distribution in
the audience. It’s not just about drugs, it is also about cells. My colleagues Margo Mar
Pershell and Chris Pershell, we discovered cells that can restore function when we transplant
them in chronic spinal cord injury that look like they may be useful in treating Parkinson’s
disease. So, we’re on the cusp of changing the way we treat horrible diseases. But given
the challenges we face with federal funding, these treatments and cures will not come quickly.
People will suffer and die needlessly. So, I’d like to ask you to remember this one equation.
If you remember anything from what I said. The velocity of scientific progress equals
discovery times dollars. Well, these days we have to re-write the equation. The velocity
of scientific progress equals discovery times donations. And don’t worry, the development
office has assured me there not going to corral you today here but when they come to you help
us build a medicine by the twenty first century.

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