Beating Alzheimer's Brick by Brick
http://triblocal.com/evanston/community/stories/2011/04/beating-alzheimer’s-‘brick-by-brick’/
Alzheimer’s disease breaks down the brain cells, dismantling memory and mental functions in a slow, brick-by-brick process.
Generating those cells and helping to find a treatment for the disease is the work of Northwestern University neurologist John A. Kessler, MD, a leading researcher and advocate for stem cell research.
Kessler and his colleagues at Northwestern's Feinberg School of Medicine have uncovered ways to use stem cells and even skin cells to create the very brain cells that people lose during Alzheimer’s. Now they're using these cells to screen for drugs that might potentially be helpful in combating the disease, and to study how they might keep these cells alive in patients. There is no treatment yet, but brick by brick, his team is building toward one.
At one time, Kessler was researching ways to understand and treat nerve disorders such as neurological conditions relating to diabetes. But when a skiing accident paralyzed his then 15-year-old daughter several years ago, he shifted his focus to spinal cord injuries and neurodegenerative diseases. Kessler explains why stem cell research is critical to treating such conditions and saving lives, and why he considers human embryonic stem cells the "gold standard."
Q. What is the ultimate goal of your research involving human embryonic stem cells?
A. My own personal quest is to use stem cells to try to regenerate the nervous system. Some of my colleagues are trying to use stem cells to try to regenerate the heart. There are different people trying to use stem cells for many different kinds of missions, but the overwhelming unifying theme is to alleviate suffering, to cure disease, to preserve life.
There has been a lot of controversy about the human embryonic stem cell field. A lot of people have made different kinds of arguments about whether we should be creating these cells. And one of the points I’ve tried to make from the very beginning is that stem cell research is about saving life, preserving life and helping people. People say, “You have to destroy a blastocyst [a fertilized egg] to make a stem cell line,” or “You’re destroying life.” But a point of fact is that we’re not destroying life. What we’re really doing is trying to preserve life. That’s the whole goal of this.
There are at least a half million frozen blastocysts sitting in in vitro fertilization centers. They will either sit in liquid nitrogen where they will eventually die, or if no one wants to pay to store them, they will get thrown into the trash. I always try to make the point that I find it hard to believe that it is morally or ethically superior to throw them in the trash rather than to allow scientists to use them to try to cure a disease.
Q. In your research, you use human embryonic stem cells to generate basal forebrain cholinergic neurons, which are lost in people with Alzheimer’s. What exactly are BFCNs?
A. In the nervous system, the cell that’s electrically excitable and does all the real work in the brain is called a neuron. Very early in the Alzheimer’s disease, there’s a group of neurons that die called basal forebrain cholinergic neurons, or BFCNs. There are two important things to know about them: First, they die very early in Alzheimer’s disease and second, they are very critical to memory function.
Q. Based on your research, how might generating BFCNs with human embryonic stem cells potentially treat people with Alzheimer’s disease and other neurodegenerative diseases?
A. The human embryonic stem cell is an exciting cell because it allows us to be able to make every single cell type in the body. We decided a number of years ago that we wanted to try to use human embryonic stem cells to generate BFCNs. Why? For two very important reasons: First, we can take these cells we’ve made and screen many drugs at the same time. We know that these cells die, so let’s put them in conditions that they won’t do well in and see which drugs help keep them alive.
If you’re trying to find a drug to cure Alzheimer’s disease, you can’t screen 10,000 drugs in actual patients and there aren’t very effective animal models, but you can do what is called high-throughput screening to test all these drugs at once on BFCNs to try to identify drugs that will be useful.
Secondly, now that we have human cells in the dish right in front of us, we can study what it is that makes them die. And in a more rational way, not just through screening, we can figure out what we have to do to keep them from dying in patients.
That takes us to the next step of what we’ve done, what’s known as the induced pluripotent [multipurpose] stem cell. The IPS cell is where you take a cell, for example a skin cell, put several genes into it and convert it into a cell that’s pluripotent – very much like a human embryonic stem cell. Why is this important? Because what we’ve done is taken skin cells from patients with Alzheimer’s disease and skin cells from patients without the disease and made IPS cells from both groups. So now we can actually find out how the Alzheimer neuron differs from the normal neurons. I can tell you from our very early studies we’re immediately finding some differences, which is surprising. We thought it would be very hard to find differences.
Finding out why cells die and finding drugs to keep them from dying is something that can stop the disease in its tracks, which is why everyone is so excited about this. We have an exceedingly potent new tool for studying the Alzheimer’s disease process.
Q. How far away are researchers from obtaining a treatment for Alzheimer’s?
A. So far, these are all big steps that we’ve made. Each time we take a step, we’re getting closer to our goal. We don’t have the treatment yet. I try to be very cautious and tell people that we don’t yet have the treatment.
If we identified a drug tomorrow that might be a good candidate, it would about 10-15 years before it was available to everyone. If you simply look at the process for drug development, that’s the average for how long it takes for the Food and Drug Administration. And we don’t even have a drug yet!
I often use this analogy: science is like building a building. You can’t just say you want a 50-story building and then start building the 50th floor first. It doesn’t work that way. Your goal is to get to that 50th story, but you have to build brick by brick. Then others can come along and start building on top of that brick. That’s how science works. I believe this will be one of those bricks that gets people closer to that goal. The beauty of science is once you put a brick in place, it’s there forever.
Content provided by Northwestern University’s Science in Society e-magazine, connecting science to you. Read other articles, find local events, or check out our blog at http://scienceinsociety.northwestern.edu/.
Story by Priscilla Kunamalla, graduate student reporter, Medill School of Journalism, Northwestern University
http://triblocal.com/evanston/community/stories/2011/04/beating-alzheimer’s-‘brick-by-brick’/
Alzheimer’s disease breaks down the brain cells, dismantling memory and mental functions in a slow, brick-by-brick process.
Generating those cells and helping to find a treatment for the disease is the work of Northwestern University neurologist John A. Kessler, MD, a leading researcher and advocate for stem cell research.
Kessler and his colleagues at Northwestern's Feinberg School of Medicine have uncovered ways to use stem cells and even skin cells to create the very brain cells that people lose during Alzheimer’s. Now they're using these cells to screen for drugs that might potentially be helpful in combating the disease, and to study how they might keep these cells alive in patients. There is no treatment yet, but brick by brick, his team is building toward one.
At one time, Kessler was researching ways to understand and treat nerve disorders such as neurological conditions relating to diabetes. But when a skiing accident paralyzed his then 15-year-old daughter several years ago, he shifted his focus to spinal cord injuries and neurodegenerative diseases. Kessler explains why stem cell research is critical to treating such conditions and saving lives, and why he considers human embryonic stem cells the "gold standard."
Q. What is the ultimate goal of your research involving human embryonic stem cells?
A. My own personal quest is to use stem cells to try to regenerate the nervous system. Some of my colleagues are trying to use stem cells to try to regenerate the heart. There are different people trying to use stem cells for many different kinds of missions, but the overwhelming unifying theme is to alleviate suffering, to cure disease, to preserve life.
There has been a lot of controversy about the human embryonic stem cell field. A lot of people have made different kinds of arguments about whether we should be creating these cells. And one of the points I’ve tried to make from the very beginning is that stem cell research is about saving life, preserving life and helping people. People say, “You have to destroy a blastocyst [a fertilized egg] to make a stem cell line,” or “You’re destroying life.” But a point of fact is that we’re not destroying life. What we’re really doing is trying to preserve life. That’s the whole goal of this.
There are at least a half million frozen blastocysts sitting in in vitro fertilization centers. They will either sit in liquid nitrogen where they will eventually die, or if no one wants to pay to store them, they will get thrown into the trash. I always try to make the point that I find it hard to believe that it is morally or ethically superior to throw them in the trash rather than to allow scientists to use them to try to cure a disease.
Q. In your research, you use human embryonic stem cells to generate basal forebrain cholinergic neurons, which are lost in people with Alzheimer’s. What exactly are BFCNs?
A. In the nervous system, the cell that’s electrically excitable and does all the real work in the brain is called a neuron. Very early in the Alzheimer’s disease, there’s a group of neurons that die called basal forebrain cholinergic neurons, or BFCNs. There are two important things to know about them: First, they die very early in Alzheimer’s disease and second, they are very critical to memory function.
Q. Based on your research, how might generating BFCNs with human embryonic stem cells potentially treat people with Alzheimer’s disease and other neurodegenerative diseases?
A. The human embryonic stem cell is an exciting cell because it allows us to be able to make every single cell type in the body. We decided a number of years ago that we wanted to try to use human embryonic stem cells to generate BFCNs. Why? For two very important reasons: First, we can take these cells we’ve made and screen many drugs at the same time. We know that these cells die, so let’s put them in conditions that they won’t do well in and see which drugs help keep them alive.
If you’re trying to find a drug to cure Alzheimer’s disease, you can’t screen 10,000 drugs in actual patients and there aren’t very effective animal models, but you can do what is called high-throughput screening to test all these drugs at once on BFCNs to try to identify drugs that will be useful.
Secondly, now that we have human cells in the dish right in front of us, we can study what it is that makes them die. And in a more rational way, not just through screening, we can figure out what we have to do to keep them from dying in patients.
That takes us to the next step of what we’ve done, what’s known as the induced pluripotent [multipurpose] stem cell. The IPS cell is where you take a cell, for example a skin cell, put several genes into it and convert it into a cell that’s pluripotent – very much like a human embryonic stem cell. Why is this important? Because what we’ve done is taken skin cells from patients with Alzheimer’s disease and skin cells from patients without the disease and made IPS cells from both groups. So now we can actually find out how the Alzheimer neuron differs from the normal neurons. I can tell you from our very early studies we’re immediately finding some differences, which is surprising. We thought it would be very hard to find differences.
Finding out why cells die and finding drugs to keep them from dying is something that can stop the disease in its tracks, which is why everyone is so excited about this. We have an exceedingly potent new tool for studying the Alzheimer’s disease process.
Q. How far away are researchers from obtaining a treatment for Alzheimer’s?
A. So far, these are all big steps that we’ve made. Each time we take a step, we’re getting closer to our goal. We don’t have the treatment yet. I try to be very cautious and tell people that we don’t yet have the treatment.
If we identified a drug tomorrow that might be a good candidate, it would about 10-15 years before it was available to everyone. If you simply look at the process for drug development, that’s the average for how long it takes for the Food and Drug Administration. And we don’t even have a drug yet!
I often use this analogy: science is like building a building. You can’t just say you want a 50-story building and then start building the 50th floor first. It doesn’t work that way. Your goal is to get to that 50th story, but you have to build brick by brick. Then others can come along and start building on top of that brick. That’s how science works. I believe this will be one of those bricks that gets people closer to that goal. The beauty of science is once you put a brick in place, it’s there forever.
Content provided by Northwestern University’s Science in Society e-magazine, connecting science to you. Read other articles, find local events, or check out our blog at http://scienceinsociety.northwestern.edu/.
Story by Priscilla Kunamalla, graduate student reporter, Medill School of Journalism, Northwestern University