Dr. Terry Heiman-Patterson is a neurologist who has dedicated her professional life to improving ALS care and advancing ALS research. She founded one of the first multidisciplinary clinics in the country in 1982 and now leads her clinic team at the MDA/ALS Center of Hope at Temple University. For her contributions to ALS care and research, Dr. Heiman-Patterson has received the Lou Gehrig Memorial Award and the Forbes Norris Award.
Your ALS Guide interviewed Dr. Heiman-Patterson at her clinic in Philadelphia on April 18, 2023.
|
“I reassure folks with ALS and their families that our team is now their extended family—and we're going to be there throughout the course of the illness.”
Why have you dedicated your career to ALS?
After my neurology training and fellowship in neuromuscular diseases, I joined the faculty at the then Hahnemann Medical School. I was the new kid on the block when a colleague asked me to see a young woman in the ICU they suspected had ALS. She was having trouble breathing and they were about to put her on a ventilator.
I did the workup and sure enough, it was ALS. I sat down to talk with her, and I explained the disease. I was 27 and not experienced at discussions about ALS. I explained that we don't have a treatment, and that it doesn't get better. She looked me in the eye and said, "I'm 38 years old and I am getting ready to go on my second honeymoon when my boys graduate. And now you tell me I'll never hold my husband again."
I just broke down. I went home and held my husband. At that moment I knew that was the rest of my career. That was where I had to make a difference. And I can't stop until I feel like I've done that. That's why I'm still in it. Because I don't feel like I've done enough.
I did the workup and sure enough, it was ALS. I sat down to talk with her, and I explained the disease. I was 27 and not experienced at discussions about ALS. I explained that we don't have a treatment, and that it doesn't get better. She looked me in the eye and said, "I'm 38 years old and I am getting ready to go on my second honeymoon when my boys graduate. And now you tell me I'll never hold my husband again."
I just broke down. I went home and held my husband. At that moment I knew that was the rest of my career. That was where I had to make a difference. And I can't stop until I feel like I've done that. That's why I'm still in it. Because I don't feel like I've done enough.
How did you start one of the first ALS clinics?
After diagnosing my first patient in 1982, I started to think about how to best take care of people with ALS. There weren't very many people at that time whose passion was to take care of people with ALS. I thought about it, did some reading, and realized that the best way to take care of people living with ALS is a one-stop shop, which is a multidisciplinary approach, where we have physical therapy, occupational therapy, speech pathology, respiratory, and mental health all in one place, with a nurse coordinator and somebody who does case management.
So I worked to put together the team and in 1984 started my first multidisciplinary clinic. I wasn't the first, but I was early in the game. And ever since that time, I've run a multidisciplinary clinic.
So I worked to put together the team and in 1984 started my first multidisciplinary clinic. I wasn't the first, but I was early in the game. And ever since that time, I've run a multidisciplinary clinic.
What are the advantages of multidisciplinary care?
It's been shown to improve quality of life—as well as survival. And now that we have medications available that slow the disease down, it's important to be able to administer them properly. It also provides a place for clinical research, which is going to be the only way we're going to make progress.
Imagine if you go to your neurologist. First of all, you hope that he knows how to make the diagnosis that he learned about in neurology residency. If he makes the diagnosis, does he know all the newest drugs? Is he savvy? And then he has to refer you out for the specialized care. |
|
So imagine your local neurologist referring you to PT over there, and OT over there, and speech over there, and the pulmonologist over here, who then sends you to the hospital to get your breathing test. Whereas you come to a multidisciplinary clinic and it's one stop. Now maybe you can do all those trips early in the disease, but later in the disease, it's a little more difficult.
And the therapists that you're seeing—they're people who have been taking care of ALS folks for years. That's what they do. Whereas you go to the local physical therapist at the PT place down the block, they've seen one other ALS person in their life. So the expertise that you build up, and the knowledge—you lose that advantage if you're not going to a multidisciplinary clinic. In my own clinic, we have more than 150 years of cumulative experience in the disease. You can't get that unless you're at a center where people really are focused on your care—on ALS care.
And the therapists that you're seeing—they're people who have been taking care of ALS folks for years. That's what they do. Whereas you go to the local physical therapist at the PT place down the block, they've seen one other ALS person in their life. So the expertise that you build up, and the knowledge—you lose that advantage if you're not going to a multidisciplinary clinic. In my own clinic, we have more than 150 years of cumulative experience in the disease. You can't get that unless you're at a center where people really are focused on your care—on ALS care.
How have you seen ALS research evolve over the years?
When I started 40 years ago, no one was interested. I was constantly asked, “Why are you doing ALS?” There weren't really any clinical trials and very little research. Over the past 40 years, there’s been an explosion of research in many different areas.
If you look at the genes identified for familial ALS, the first was identified in 1993. A couple years later, there was another and then another. In the last eight years, probably 25 have been identified because technology has advanced to the point where we can sequence whole genomes and do the statistical analysis necessary to identify changes in the DNA.
So, I have these 30 genes. And they point to different pathways in the body that when damaged can lead to motor neuron damage. We've identified at least ten pathways, even in people without a family history. So they're overlapping. I always say we're learning about motor neuron biology and motor neuron disease gene by gene.
This overlap between the familial cases with genetic changes and sporadic ALS where there are no genetic abnormalities suggests that these pathways are relevant to both sporadic and familial ALS. The pathways implicated by affected genes gives us clues to what pathways to target for treatment.
The other exciting thing is we've got three drugs now. They were found by looking at these implicated pathways where when something goes wrong, it kills a motor neuron. We get drugs that modify those pathways and we try them and we see if they help people with the disease. And so we have drugs that modify neuro inflammation. We already know the drugs that modify oxidative stress can help. Drugs that modify glutamate excitotoxicity can help. Drugs that provide nutrition to neurons or reduce the toxic effects on mitochondria can help.
So we're testing each of those pathways and that's exciting. And then the other component in parallel is the identification of biomarkers.
If you look at the genes identified for familial ALS, the first was identified in 1993. A couple years later, there was another and then another. In the last eight years, probably 25 have been identified because technology has advanced to the point where we can sequence whole genomes and do the statistical analysis necessary to identify changes in the DNA.
So, I have these 30 genes. And they point to different pathways in the body that when damaged can lead to motor neuron damage. We've identified at least ten pathways, even in people without a family history. So they're overlapping. I always say we're learning about motor neuron biology and motor neuron disease gene by gene.
This overlap between the familial cases with genetic changes and sporadic ALS where there are no genetic abnormalities suggests that these pathways are relevant to both sporadic and familial ALS. The pathways implicated by affected genes gives us clues to what pathways to target for treatment.
The other exciting thing is we've got three drugs now. They were found by looking at these implicated pathways where when something goes wrong, it kills a motor neuron. We get drugs that modify those pathways and we try them and we see if they help people with the disease. And so we have drugs that modify neuro inflammation. We already know the drugs that modify oxidative stress can help. Drugs that modify glutamate excitotoxicity can help. Drugs that provide nutrition to neurons or reduce the toxic effects on mitochondria can help.
So we're testing each of those pathways and that's exciting. And then the other component in parallel is the identification of biomarkers.
Why are biomarkers important?
There are probably going to be biomarkers that we're going to discover that will help us identify different groups. A group in which inflammation is driving disease, a group in which oxidative stress is driving disease. And that's going to determine what the best sort of concoction is going to be to treat their disease. Much like cancer, you can have different flavors of breast cancer, and depending on the pathology, and the receptor types, that's going to determine what therapies are going to work best for you. We don't have that yet in ALS, and we need that.
But it's only through multidisciplinary care, and multidisciplinary centers where you also do clinical research, and collect large numbers of folks living with ALS, that you'll be able to get enough samples, and enough clinical data to tie those together, and to begin to stratify, which is so important.
But it's only through multidisciplinary care, and multidisciplinary centers where you also do clinical research, and collect large numbers of folks living with ALS, that you'll be able to get enough samples, and enough clinical data to tie those together, and to begin to stratify, which is so important.
What’s on the horizon for ALS research?
I need to be able to characterize an individual's disease to personalize treatment. I need to characterize what's driving your disease, what pathway, and where you are in the disease course.
Say pathway A initiates it, pathway B drives your disease, and pathway C is endgame. If you're in the middle of your disease, I need to target pathway B. It's too late to target pathway A and too early to target pathway C, although I can do that too, because maybe it'll slow it down there. But I need to target where you are in your disease and I need to know what started it and whether that's still active. |
|
And I need to be able to stratify you for clinical trials. I need to predict what person will respond to what drug. So when I do a clinical trial, positive results aren't washed out by those people included who would not be predicted to respond to the drug under study. We may have thrown out a lot of good drugs because we tried them on a large population that included only a small percentage of people whose disease was driven by the pathway targeted by the drug in the trial.
Imagine drug A works on mechanism X and I have 100 people, but only 20 of them have mechanism X that's operating. And I give this drug to all 100 people, well, it's only going to work on the 20 whose disease is caused by pathway X. Thus, when I look at the results in all 100 people, those positive results may be overshadowed or washed out by the negative ones in the 80 people.
So, until I can personalize a little bit more or stratify better, I may be throwing out good drugs for a segment of the population. But we're getting there. We're learning these things. We're learning a lot from the way cancer operated and developed. And we're trying to apply some of that to ALS, although it's a heterogeneous disease. And I think that's exciting.
So, biomarkers, druggable pathways, and new ways to do clinical trials.
The HEALEY Platform Trial allows us to test multiple drugs with a single placebo group and do it faster. What used to take 12 years takes two years. That means I can test multiple drugs faster. So if they're good, great, I get them home faster. There are less people getting a sugar pill because everybody shares a placebo group. So you need less people getting placebo. So that's good.
Imagine drug A works on mechanism X and I have 100 people, but only 20 of them have mechanism X that's operating. And I give this drug to all 100 people, well, it's only going to work on the 20 whose disease is caused by pathway X. Thus, when I look at the results in all 100 people, those positive results may be overshadowed or washed out by the negative ones in the 80 people.
So, until I can personalize a little bit more or stratify better, I may be throwing out good drugs for a segment of the population. But we're getting there. We're learning these things. We're learning a lot from the way cancer operated and developed. And we're trying to apply some of that to ALS, although it's a heterogeneous disease. And I think that's exciting.
So, biomarkers, druggable pathways, and new ways to do clinical trials.
The HEALEY Platform Trial allows us to test multiple drugs with a single placebo group and do it faster. What used to take 12 years takes two years. That means I can test multiple drugs faster. So if they're good, great, I get them home faster. There are less people getting a sugar pill because everybody shares a placebo group. So you need less people getting placebo. So that's good.
Tell us about the recent advances in genetics.
The things that I'm really excited about coming down the pike in the future are drugs that modify genetic changes, or ways to alter genetic changes. And 10% of ALS is familial. In that familial group, we can identify genetic abnormalities in 70% and we're now up to more than 30 genes that, when damaged, can cause an ALS clinical picture.
The most common is the C9ORF72, or C9 for short. It's a gene in which there's extra DNA that doesn't belong there. And there are now strategies to approach that. We don't have anything that's working quite yet, but there are clinical trials going on. We hope it'll work. And this damaged gene can actually present not only as ALS, but as frontotemporal dementia or both in the same person. But we're actually at that stage where we're manipulating genes and trying to cure and change diseases.
The second mutation is the one that was identified first, SOD1, which was identified in 1993. That was the first gene ever identified. And we now have a gene therapy that's waiting for approval at the FDA. [Update: Shortly after this interview, the FDA granted accelerated approval for tofersen in April 2023.]
Then it brings up a whole other population of folks. What am I going to do for people who are in families with these genes who are identified as carriers of the genes? If I slow a disease down using a treatment, do I want to start it as early as possible? Maybe even before you start to show disease?
I don't know the answer yet, but I think we have to figure out the answers to when do you start. How do we care for people who are living with that specter of ALS hanging over them? And what advice should we give? And if there are drugs available, should we be using them? I'm not saying I know the answers, but I certainly know the questions that we have to be asking.
The most common is the C9ORF72, or C9 for short. It's a gene in which there's extra DNA that doesn't belong there. And there are now strategies to approach that. We don't have anything that's working quite yet, but there are clinical trials going on. We hope it'll work. And this damaged gene can actually present not only as ALS, but as frontotemporal dementia or both in the same person. But we're actually at that stage where we're manipulating genes and trying to cure and change diseases.
The second mutation is the one that was identified first, SOD1, which was identified in 1993. That was the first gene ever identified. And we now have a gene therapy that's waiting for approval at the FDA. [Update: Shortly after this interview, the FDA granted accelerated approval for tofersen in April 2023.]
Then it brings up a whole other population of folks. What am I going to do for people who are in families with these genes who are identified as carriers of the genes? If I slow a disease down using a treatment, do I want to start it as early as possible? Maybe even before you start to show disease?
I don't know the answer yet, but I think we have to figure out the answers to when do you start. How do we care for people who are living with that specter of ALS hanging over them? And what advice should we give? And if there are drugs available, should we be using them? I'm not saying I know the answers, but I certainly know the questions that we have to be asking.
What about the value of non-drug interventions?
Treatment is more than just drugs that slow the disease down. It's great. We have three now, that is so terrific. When I started 40 years ago, we had zero. And so what I've seen over 40 years is nothing short of exciting, although it's never fast enough for someone living with ALS, and I get that.
But I'm so excited about the evolution of drug treatment that slows the disease down. Drugs are coming online and that's really exciting. But you know what? There are other things that make a heck of a lot of difference to people living with ALS, both in terms of quality of life and survival. |
|
First of all, symptom management. The drugs that slow the disease down don't help your drooling, and they don't help your cramps, and they don't help your constipation. And so we have medical management of the symptoms that makes a huge difference for quality of life. And it's really important, as mundane as it is, to talk about that with the person caring for you if you have ALS, and to go through what symptoms you're having. What is it that's really keeping you up at night, so to speak. Because we do have approaches.
The second thing, which is in a way symptom management—but I look at it as an intervention—is BiPAP, or non-invasive ventilation. It supports your respiratory muscles and your ventilation. It allows the respiratory muscles to rest and it improves the exchange of oxygen and carbon dioxide. In utilizing non-invasive ventilation at the appropriate time, it extends life upwards of 14 months.
That is better than any of my drugs at this moment. People have less fatigue and they feel better, and you think better, so cognition is also improved. So something as mundane as non-invasive ventilation makes a huge difference—and properly applying that, and knowing when.
And then there's of course intervention for nutrition. That's also quite important, because if you get dehydrated or you're malnourished, you're going to get weaker faster. So appropriate nutrition is really important. It's been shown that the higher your BMI at the beginning, the better you do long term. So for those of us who are a little overweight, guess what? We do better with ALS. Nutrition can be hugely important, and unfortunately we don't have enough research in that area about what's the best nutrition. We know that there may be differences in different types of feeds. For instance, high fat and high carb may make a difference in survival, and there's some work being done there.
Please don't misinterpret me. I'm so excited about the drugs, but don't lose sight of what good care means, and good care is done best by people who are experienced. Again, we're back to multidisciplinary care for the most part.
The second thing, which is in a way symptom management—but I look at it as an intervention—is BiPAP, or non-invasive ventilation. It supports your respiratory muscles and your ventilation. It allows the respiratory muscles to rest and it improves the exchange of oxygen and carbon dioxide. In utilizing non-invasive ventilation at the appropriate time, it extends life upwards of 14 months.
That is better than any of my drugs at this moment. People have less fatigue and they feel better, and you think better, so cognition is also improved. So something as mundane as non-invasive ventilation makes a huge difference—and properly applying that, and knowing when.
And then there's of course intervention for nutrition. That's also quite important, because if you get dehydrated or you're malnourished, you're going to get weaker faster. So appropriate nutrition is really important. It's been shown that the higher your BMI at the beginning, the better you do long term. So for those of us who are a little overweight, guess what? We do better with ALS. Nutrition can be hugely important, and unfortunately we don't have enough research in that area about what's the best nutrition. We know that there may be differences in different types of feeds. For instance, high fat and high carb may make a difference in survival, and there's some work being done there.
Please don't misinterpret me. I'm so excited about the drugs, but don't lose sight of what good care means, and good care is done best by people who are experienced. Again, we're back to multidisciplinary care for the most part.
Is there anything else you would like to say?
When I see new people with ALS and I'm talking to them, I think it's really important to stress hope. It's important to explain the disease and how I came to the diagnosis. I think education is a critical piece. I talk about the motor system and how we classify motor neuron diseases and why I think they might have this disease ALS, so that they understand.
|
|
I think it's important to understand why Dr. X just looked at them, didn't do any tests, and said, you have ALS. By explaining how we make the diagnosis, it gives some sense of closure about the diagnosis, and I also in the same breath say, "I’ve got to rule out anything that could possibly be causing the damage." And we do as complete a workup as I think is necessary to make sure nothing is mimicking ALS.
The second piece is, okay, if this is ALS, what can we do? We can do a lot. I’ve got drugs that slow it down. I have good clinical care and a multidisciplinary approach that can really maximize function, and I've got clinical trials and that gives us hope for newer drugs.
And I say, “I don't have a crystal ball. The average disease is three to five years. But what you didn't read—and I think is important—is that 20% of people live more than five years, and 10% more than 10 years.” I try to stress that my job is to put you in that 10% with the tools we have now and the tools that are going to develop over the next few years.
I also explain that this disease is going to affect the whole family. This is a family disease, no question. And I reassure folks with ALS and their families that our team is now their extended family—and we're going to be there throughout the course of the illness, and they'll have our phone numbers and our emails and we want to hear if there's something we can help with and some way we can help them negotiate this difficult path that they're on.
The second piece is, okay, if this is ALS, what can we do? We can do a lot. I’ve got drugs that slow it down. I have good clinical care and a multidisciplinary approach that can really maximize function, and I've got clinical trials and that gives us hope for newer drugs.
And I say, “I don't have a crystal ball. The average disease is three to five years. But what you didn't read—and I think is important—is that 20% of people live more than five years, and 10% more than 10 years.” I try to stress that my job is to put you in that 10% with the tools we have now and the tools that are going to develop over the next few years.
I also explain that this disease is going to affect the whole family. This is a family disease, no question. And I reassure folks with ALS and their families that our team is now their extended family—and we're going to be there throughout the course of the illness, and they'll have our phone numbers and our emails and we want to hear if there's something we can help with and some way we can help them negotiate this difficult path that they're on.