Here is the full transcript of Michael C. Levin’s talk titled “Can We Stop MS And ALS?” at TEDxUniversityofSaskatchewan conference.
SUMMARY: Dr. Michael C. Levin’s TEDx talk, “Can We Stop MS and ALS?” presents an insightful exploration into the mechanisms of nerve cell function and the impact of diseases like Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) on these cells. He begins by engaging the audience with a simple exercise to demonstrate how nerve cells communicate from the brain to the toes, highlighting the complexity of this process and the challenges faced by individuals with MS.
Levin discusses the pathology of MS, focusing on the deterioration of nerve cells and the role of the protein A1 in this process. Through years of dedicated research, his team discovered and developed medications that could potentially reverse the damage caused by MS, as demonstrated in laboratory nerve cells and mice models. These groundbreaking findings not only offer hope for halting MS but also suggest potential therapeutic strategies for ALS, given the similarities in nerve cell damage.
Levin’s talk emphasizes the significance of understanding the underlying causes of neurological diseases to develop effective treatments. His optimistic outlook on the future of MS and ALS treatment inspires hope for patients, researchers, and healthcare professionals alike.
Listen to the audio version here:
TRANSCRIPT:
How Do Nerve Cells Work?
How do nerve cells work? And to begin to understand how nerve cells work, let’s use our nerve cells. I’d like everyone to wiggle their toes. I’m going to wiggle my toes. What just happened? Well, what you just did is you signaled a nerve cell in the front of your brain, and that nerve cell sends a branch all the way down to your spinal cord, where it talks to a second nerve cell, and that nerve cell sends a branch, also known as an axon, down to your toes, and your toes wiggle, something we all take for granted.
But if you have multiple sclerosis, or MS, this can be very difficult to do, and some days even impossible to do. And the question is why?
Understanding Multiple Sclerosis
And the answer is because nerve cells in people with MS are sick. Now, this is a sick nerve cell. How can we tell? It’s alone. Nerve cells in our bodies work in groups, tens, hundreds, thousands, even millions, probably millions, to just wiggle our toes.
Second, its branch, known as an axon, is small. And if you look closely, the axon is bright. The nerve cell it’s connected to is bright. But the connection between the two is less bright. This axon is hanging on for dear life. Well, here we discovered how this happens. We discovered how MS nerve cells get sick.
And then we invented medicines to prevent it. And then we fed these same nerve cells those medicines, and this is what we saw. And it still takes my breath away. A field full of nerve cells. So many nerve cells, you can’t tell where one starts and one stops. Axons that are long and beautiful and communicating with other nerve cells and doing their jobs. And it is because of this discovery that we think we can stop MS in its tracks. And we’ve learned something so basic, so fundamental about how nerve cells work, we think this is going to help people with other neurologic diseases, like amyotrophic lateral sclerosis, or ALS.
The Journey to Discovery
So it took me 30 years to get here. I have 10 minutes to tell my story. Let’s get started. MS is a big problem. Almost 3 million people globally have MS. And in this heat map, where dark red shows the highest rates of MS in the world, you can see Saskatchewan has a very high rate of multiple sclerosis. Not only one of the highest rates in Canada, but one of the highest rates in the world.
So what does that mean? That means everyone in Saskatchewan knows somebody with MS. In fact, everyone in Saskatchewan probably knows two people with MS, including a family member and that person’s best friend who’s lived down the street. So if you know anyone with MS, raise your hand. I know hundreds of people with MS.
Living with MS
And I can tell you I’ve spent most of my career telling people they have MS, and that is a life-altering experience. So what’s it like to have MS? So over time, following the blue line from left to right, people with MS get disabled. It’s not a smooth road. It’s bumpy. As shown by those blue columns, each one of those blue columns is an attack of neurologic dysfunction, and those are called relapses. And they happen randomly through someone’s life.
And if I can bring your attention to the first two columns, you’ll see after the first column, after a relapse, people come back to baseline, sometimes even normal, and that’s called a remission. And that’s where the term relapsing, remitting, multiple sclerosis comes from, the most common form of MS.
So what is an MS relapse? One day you might have blurred vision in one eye. The next time, both legs may become numb or even paralyzed, or you may have acute bouts of pain, all leading to decreased quality of life, trouble with employment, difficulty with intimacy, difficulty with mobility, all the things most of us take for granted.
Well, I remember when I met my first MS patient, and it was 1990. I was a first-year neurology resident at New York Hospital in New York City, and the wards were filled with patients with stroke and dementia. But it was the MS patients that interested me the most. They actually chose to be admitted to the hospital over a weekend.
A Personal Journey Through MS Research
So those relapses I talked to you about, back then and even now, we treat with high-dose steroids, 1,000 milligrams of steroids for three consecutive days.
So they’d come in the hospital Friday, Saturday, Sunday, and they would wake up Monday morning in the hospital, get dressed, and go to work. It’s inspirational. And they inspired me to choose to take care of people with MS for the rest of my life and to do research into the cause and cure for MS.
So my next stop was at NIH. And it is there where you can see we had several successful experiments. But it was at NIH where I first saw that a neurocell protein was abnormal in MS. It’s also when I started my family with my lovely wife, Audrey, and if you read my bio, I have two strappingly handsome sons.
And I’m told if I leave this up any longer, I probably won’t be forgiven. So here they are now, and I want to thank my family for the love and support they’ve given me throughout this extraordinary journey.
I then next landed in Memphis, Tennessee, home of Elvis Presley. And at the University of Tennessee, and at the neighboring Veterans Repair and Medical Center, it’s where I discovered what the abnormal MS protein was, heterogeneous, nuclear, ribonucleoprotein A1, or A1 for short. And that was published in one of the world’s premier manuscripts called Nature Medicine.
Now here I am in Saskatchewan, where some days it’s colder than it is on Mars. But it is here at the University of Saskatchewan where I made the seminal discovery of how A1 malfunction causes neurocells to be sick, and invented medications to stop it. Now to understand how A1 works, we have to do a little bit of neuroscience.
And I’m a neuroscientist, and neuroscientists love to look at things under microscopes. And here we are looking at high power view of human brain. And on the left we see healthy brain. And we see five large brown triangular cells, and these are nerve cells. You can see this is different in brains of people with MS, shown on your right where there’s nerve cell loss and nerve cell injury.
So what’s the problem? People with MS get worse. We give them anti-inflammatory drugs, and we wipe out the relapses, but people with MS still get worse. And the question is why? And the answer is nerve cell loss. Nerve cells get sick and injured throughout a person’s life if you have MS. So I told you MS is inflammatory.
So you block the inflammatory system, you block inflammation from entering the brain, and you cure MS. That’s what I was taught, and that’s probably what you read. Well, it’s just not true. We look at MS differently here at the University of Saskatchewan. We look at it from the point of view of the nerve cell, and we ask the question, how would you protect that nerve cell, and how is it being injured? And this is the discovery we made.
That protein A1 we just spoke about gets stuck in the wrong part of the cell. So here we are again looking at human brain. Two nerve cells, you can see the nucleus or the center of each cell, and A1 is stained in brown. The surrounding area of the nerve cells is called the cytoplasm. Very difficult to see, so I drew it. And you can see almost all the A1 is in the nucleus, and none is in the cytoplasm.
The Revolutionary Findings and Future Outlook
Let’s see what happens with MS. And I want to bring your attention to the nucleus of these two nerve cells. There’s no A1 in the nerve cells. And if you look closely at the brown dots, all of the A1 is in the cytoplasm. And it’s that clip, it’s that change of 180, where A1 was in the nucleus, and now there’s none in the nucleus in MS, and it’s all stuck in the cytoplasm, that triggers nerve cell injury and nerve cells to become sick.
So what do we do about it? We can grow nerve cells in the lab. These are nerve cells grown in a lab in a dish. You can see 1, 2, 3, 4, 5 cells, and A1 is bright green in the nucleus. And the arrows show that A1 is in the cytoplasm. So we stress these cells, just like MS nerve cells are stressed. And we don’t have to move all the A1 into the cytoplasm like I showed you, just a little bit.
And when we do this, what happens to the nerve cell? Well, there are less nerve cells, there’s nerve cell loss, nerve cells become sick, and axons become damaged. We then invented medications to try to prevent this. And we fed these medications to these same nerve cells. And what did we see? A1 is in green. All of the A1 is in the nucleus. All of it went back home where it belongs. And when A1 is in the nucleus of a nerve cell, that nerve cell begins to function normally again.
And what did we see? Again, a field full of nerve cells. So many nerve cells, too many to count. We don’t know where one starts and where one ends. And those long, beautiful axons are doing what they’re supposed to do. They’re communicating with each other. And when people ask me, have I ever had that aha moment in science, and this is it.
Because not only did we stop nerve cell loss, but the nerves began to multiply. Not only did we stop axons from being injured, but they regenerated. And we think this is a transformational finding. That’s nerve cells growing in a dish. Before we give these medications to people, we have to test them in mice.
So here’s what nerve cells look like in a normal mouse. A1 is in green. It’s completely in the nucleus. We give mice a disease that mimics MS. And as shown by the arrows, some of A1 gets stuck in the cytoplasm. And we feed these mice the same medications that we fed the nerve cells growing in a dish. And lo and behold, A1 goes back home in the nucleus.
And what happens to the mice? Will they get better? If I can bring your attention to the left column, the black column, you see average score in this group is 40. Higher numbers mean sicker mice. We feed the mice these medications. Their score is only 20, and they get 50% better. This might be the difference between wiggling and not wiggling your toes. This might be the difference between not being able to walk and being able to walk another day.
There’s another disease where A1 is abnormal, and that’s ALS. Now we’re at a super high-power view of human brain once again. You can see there’s no A1 in the nucleus. All of the A1 is stuck in the cytoplasm. And because this nerve cell looks so much like a nerve cell from someone from MS, we think these medications we invented will also work for people with ALS.
So we think we’ve cracked a code into how nerve cells are injured and get sick in MS. And my hope is not only our lab, but other labs around the world begin to study A1 and proteins like it to see how these nerve cells get sick so we can prevent it. So our plan in the next three to five years is to design these medications to give to people in clinical trials to stop nerve cells from being sick, to inhibit disability, to improve people’s lives with these devastating diseases, and to stop MS and ALS in their tracks. Thank you.