Paralympic Athlete Helen Kearney on Living Her Dreams with Friedreich’s Ataxia

Episode Transcript

Dr. Correa:
From the American Academy of Neurology, I'm Dr. Daniel Correa.

Dr. Peters:
I am Dr. Katy Peters, and this is the Brain and Life Podcast. So, I know we've all been watching the Olympics. I know that you've enjoyed the Olympics, Daniel, and I know one thing it does for me is it inspires me to go out there and try to be the best athlete I can be, to swim a little faster or jump a little higher. How about you?

Dr. Correa:
Just to move a little bit faster and higher. I definitely don't necessarily go try and spin and flip and do any of those things. They practice hard to do it well and not get hurt, and I appreciate that. I just try to do a little bit of extra running, get outside.

Dr. Peters:
Yes, don't get hurt. That's the key thing. Now I know that you enjoy the Olympics. Are you planning to watch the Paralympics?

Dr. Correa:
I'm definitely planning to watch them. While I was training at Walter Reed, I got to see and cheer on some of the games of the wheelchair basketball. I found the opportunities and the amazing athletic achievements by the adaptive sports program and that community really uniquely inspiring. I'm also looking forward to seeing the wheelchair race. While in New York at times either running or watching the New York City Marathon, I've seen Marcel Hug and Madison de Rozario speed past us during the New York City Marathon and it's going to be great to see their speed on the streets of Paris.

Dr. Peters:
Yeah, I plan on watching the Paralympics also, and I was really inspired by this because I got to talk to Helen Kearney. She is a Paralympic equestrian who dazzled us to win three medals at the 2021 Summer Paralympics in London, England. When she was around the age of 10, she started to learn to ride horses and she just excelled and flourished at it. Unfortunately, she did get diagnosed at the age of 13 with a rare genetic neurologic condition called Friedreich's ataxia that it can affect her balance and gait, but she continued to ride and found that with being an equestrian, she was able to have better control of her body. So, I can't wait to hear her again today and have her share her story with us.
Hello, Brain and Life Podcast listeners. I'm very excited to be joined by our guest today, Helen Kearney. She is a paralympic equestrian who dazzled us to win three medals at the 2012 Summer Paralympics in London, England. Starting at the age of 10, she began to ride horses and she excelled, hence all of those medals. Unfortunately, at the age of 13, she was diagnosed with a rare neurologic condition called Friedreich's ataxia, but this did not deter her or slow her down. I'm delighted she's joining us for the Brain and Life Podcast. Hello, Helen.

Helen Kearney:
Hi. Thanks very much for having me.

Dr. Peters:
Can you tell us a little more about yourself and where you're joining us from?

Helen Kearney:
So I'm based in Ireland. I'm just out of Dublin. I'm 34 years. I've been doing the horses for way too long and they're my shame and fame.

Dr. Peters:
That's wonderful. I mentioned equestrian dressage. Can you tell us a little more about what that is?

Helen Kearney:
Absolutely. So, dressage is you get a test that you know about in events and you know the size and layout of the arena. So, there's eight markers and the test tells you what to do with what marker and then there is five judges that sit around it and mark based on what they see. Depending on their positions, they'll be able to see different things. So, it's hard enough to get away with doing too much wrong.

Dr. Peters:
How do you train the horses?

Helen Kearney:
Everyone is really individual in that. For me, Friedreich's, it affects your whole body. It's not like it impacts one name or one thing especially. So, in general, the horses just have to be sensible and not get offended too easily, but I would describe it a bit like everything works but nothing works well. So, I can give a bit of a feel with my legs. I can use the reins. Sometimes I might do a little more or a little bit less than I mean to. That's why I just find the horses need to be able to not get offended too easily, to bear with me. Generally, in terms of training, time really helps a lot of things like that. So, for instance, one of the movements we do, we have to do a free walk and allow the horse to stretch.
Now, ideally, if you are totally everybody, you'd let the rains go a bit longer, but because of difficulty with my hands, I find it very hard to collect reins back up. So, I have to lean forward slightly and give them a little bit more room that way. But I had one horse that used to get really worried about it and think it meant go really fast. Basically, time just helped. Little by little, it started to get the idea, but that took him the best part of two years to become somewhat comfortable with it.

Dr. Peters:
I feel like that's not just good advice about horses, but good advice for people, taking a little slow with them and let them be a little calm about it. That's great advice. Do you have a particular horse you're riding with right now?

Helen Kearney:
So yeah, I do. I have a horse at the moment. I've been very lucky. I've had several horses throughout the years. The one I have now, he's a great character and he's really good in some respects, but I probably, it's fair to say, made a little bit of an error in judgment with him. He's quite big. In terms of taking them together and stuff, the judges maybe aren't quite happy that we're getting it quite right. In hindsight, I should have seen this issue coming. But look, it's always hard to find them and maybe it worked out quite well.
So, basically, I went through a very bad time with scoliosis surgery and I was off the horses for a long time. Because of that, I didn't compete for a while and we had him and I got back out competing. I actually thought he was going to do great and maybe ignorance is bliss. Even though we didn't do great, maybe it was a good thing to have him and from my head to think that we would do great even though we didn't quite fulfill that.

Dr. Peters:
I think that that sounds like a great partnership and you have to deal with each other's own challenges. What is the horse's name?

Helen Kearney:
Benny. Most horses are called one thing in the stable and then they have a posh name. So, his posh name is Sensation, but we call them Benny in the stable.

Dr. Peters:
I think we should all have a posh name and a stable name. I'll have to think of a posh name for myself. So, tell us, you did have this wonderful experience of participating in the Paralympics. It sounds very exciting. Can you tell us more about just participating and what it meant to you?

Helen Kearney:
Oh gosh, what it meant to me, it was amazing experience. So, I got involved in 2008 and I saw a few people go to Paralympics before mine, which was in Beijing. I in my head said, "Right, that's what I really want to do. I want to go the next time." Then I think because of Friedreich's, I really thought, "Okay, it's progressive. So, London is really a great chance and I'm never going to have a games as close to me as London."
So I probably was a bit laser focused, but things did fall into place right for me. Finding the right horse is actually quite difficult and I was fortunate with the way it fell. My trainer picked out the horse that I had and he turned out to be amazing, but when I rode him, I thought it was horrible. He was really difficult. I thought she was nuts, but she was like, "No, bear with me." She was dead right. I'm so glad she did say that to me.

Dr. Peters:
What were some of your favorite aspects about competing?

Helen Kearney:
I think with the horses and it being physical, it's really good for me physically in terms of managing symptoms. But I also think just in general, emotionally, being able to do something like that and get to compete at such a high level has given... I would describe it as given me a lot of what the disability takes away. It's going to give me a great reason to get up every day and to feel a good accomplishment and things like that.

Dr. Peters:
Well, I'm so happy for you. You mentioned already that you were diagnosed with Friedreich's ataxia. Can you tell us how that all happened and when you were diagnosed?

Helen Kearney:
My diagnosis was when I was 13, so 21 years ago. Shortly before my diagnosis, I had corrective surgery for scoliosis and I guess I was a bit slow recovering and there was a few things not quite right. A physio just picked up on a few things and that one thing led to another and that's how the diagnosis happened.

Dr. Peters:
Are you receiving any particular treatments right now for the Friedreich's?

Helen Kearney:
No. Well, the first treatment has been approved in states and now in Europe.

Dr. Peters:
Oh, great.

Helen Kearney:
But it hasn't quite come to Ireland yet. I think realistically it will still be another while, but it is very exciting that there is treatment out there. I think overall, I've always been very firm and move it or lose it. Exercise is really important in helping manage things. If you don't keep using things, unfortunately, you lose them.

Dr. Peters:
Does dressage help you with that? Is it part of that exercise?

Helen Kearney:
Yeah, definitely. So, it's brilliant for me in a sense that it almost doesn't feel like exercise. It feels like just something I'm doing because that's what I want. But also, I think it's probably been more important to me than I realize because with Friedreich's and with a lot of conditions, fatigue is a big one and horse riding and that allows you to be physically active without overworking. Also, it's good for the core stability. It's not so easy always to find an exercise for your core, but that in essence is basically what the worst is.
It's barely a workout for your arms and legs, but in terms of your core and helping stimulate balance, it is a good exercise. I'd say that has helped me quite a lot. Then also when I was younger, I was on my feet, much better able to. I think the physical exercise of bringing the horses or milking out or doing those jobs really helped keep me going so much more than I can ever really appreciate.

Dr. Peters:
I think that's a great lesson for all of our listeners. I just say keep on moving and keep on doing the activity. I think that helps. I didn't really realize that about the core, but I guess it's true. I guess when you're having to sit up on the horse, particularly with dressage, with the way your body has to sit on the horse, that makes a lot of sense.

Helen Kearney:
Yeah. You don't have anything behind you and you have something moving underneath you. So, you constantly, even though you don't realize it, end up working things like your glutes or your abdomen, just trying to stay on.

Dr. Peters:
That would be my first step. Stay on the horse. Any tips for staying on a horse?

Helen Kearney:
No, it's a strange feeling and this is not something that is easy to even tell someone, but when you have a horse collected and together, it's a little bit easier. How I would describe it, do you know when you are in a car with somebody and you are in the passenger seat and they break? They don't fall forward, but you do because the movement that happens is unexpected and you don't realize it, but they know because they're the ones that put their foot in the brake. So, they're less going to fall forward.
Same thing when you truly have a horse connected, staying on is awful lot easier because you know what you've asked them. You know are pushing them out or moving them over or going to turn and it's a lot easier to stay on when you are the one controlling that. Now we all strive to control it all the time and sometimes control is better than the other times, but that's in general the aim in game to have optimum control.

Dr. Peters:
Now, we talked about Friedreich's ataxia and you mentioned that new drug that's approved in both Europe and in the United States. I believe it's called omaveloxolone.

Helen Kearney:
Yeah.

Dr. Peters:
I know you're pretty excited about that new agent. Is there other hopes for the future that you have for Friedreich's ataxia?

Helen Kearney:
Definitely. There's research ongoing and the drug is showing good signs at showing progression, but it's to a varying degree. Some reports are really good, but some might not be quite as positive. So, they're still looking at other things. I think, look, that might not be in my lifetime, but definitely as they make strides towards things like gene therapy, they might find a way to reverse things as well. We're not at that point yet, but hopefully into the future, we will be.

Dr. Peters:
I agree with you. I can't wait for the future and I think that there's going to continue to be developments. Part of that future is going to be the Olympics and the Paralympics. So, I just want to say, Helen, thank you so much for this lovely interview. Thank you so much for sharing your experience and your life and teaching us all about both equestrian and also Friedreich's ataxia. So, thank you again so much.

Helen Kearney:
Thank you so much for having me. Thanks for doing this podcast. It's really great resource for people and it's nice I'm sure for people to hear different stories and find different avenues in life, because I know for me, definitely the horses and the direction things have taken me is not one I would've thought of, but it's given so much of what the disability takes away and I'm really grateful for having the experience.

Dr. Correa:
Can't get enough of the Brain and Life Podcast? Keep the conversation going on social media when you follow @neurodrcorrea and @BrainandLifeMag or visit brainandlife.org.

Dr. Peters:
Hello, Brain and Life Podcast audience. Thank you so much for joining us today. I am again, Katy Peters. I'm your cohost and I'm honored to introduce our medical expert Dr. Subramony. He is a board certified neurologist and neuromuscular medicine specialist at the Norman Fixel Institute for Neurologic Diseases at the University of Florida in Gainesville. He is a professor of neurology and has a joint appointment in pediatrics. So, we're going to learn a lot today about child neurology.
His research involves interventional and observational projects that also include first in human trials and we'll discuss that also, mainly for genetic neuromuscular diseases such as Friedreich's ataxia myotonic dystrophy, vesicular scapular humeral dystrophy, and also spinal cerebellar ataxia. So, I just want to say welcome and welcome to the Brain and Life Podcast.

Dr. Subramony:
Thank you.

Dr. Peters:
Great. Now can I give you a short introduction? Do you mind telling us a little bit more about yourself and where you're joining us from today?

Dr. Subramony:
Yes. So, as already pointed out, at the University of Florida College of Medicine and Fixel Neurological Institute. I've been a neurologist for quite some time and almost all my career I was what we call a neuromuscular physician. I've been a director of the Muscular Dystrophy Association of Clinics for a long period of time, and we also have an ataxia center of excellence here at UF, which I direct together with Dr. Burns. I've been involved in various forms of cerebellar ataxia for a long time.
My original research interest was in the spinocerebellar ataxia where I was part of the teams that discovered genes for several of those early spinocerebellar ataxia like type one, type three, and type six and have continued my interest in the field of genetic ataxia. We've come a long way in the last 30 years where we are now conducting clinical trials of novel medications in this group of genetic diseases as well as some of the muscle diseases where I have an interest, which are very similar.

Dr. Peters:
That's wonderful. You mentioned you're a neuromuscular medicine expert. For our audience, what conditions are really "neuromuscular" in neurology?

Dr. Subramony:
So there are many of us in the country who focus our interest on nerves, which are the electrical cables coming out of your back into your arms and legs, nerve and then goes into your muscles, so the way we move, we speak, use our hands. So, there are many disorders that affect muscles such as the muscular dystrophies and there are other similar disorders. That's the major interest of neuromuscular physicians. The ataxias on the other hand affect the balance part of the brain that we call the cerebellum. It sits in the back part of your brain right underneath your neck and head in that area.
When I started working on ataxia, it was an orphan field. We did not know which specialty was going to see patients with ataxia. Increasingly in this country now, the ataxia patients are being seen by what we call movement disorder neurologists. So, I have a little attachment to this group here, but I only see the ataxias. I don't see some of the other things like Parkinson's that they see as well. So, it's an orphan group of diseases that's gradually coming into focus and exciting things are happening.

Dr. Peters:
Thank you for explaining that to us. Now, we had a podcast guest, it's Paraolympian Helen Kearney, and she was diagnosed with Friedreich's ataxia. Can you tell us a little more about this specific condition?

Dr. Subramony:
Yes. So, this is a genetic condition. It's a recessively inherited condition. What that means, every gene that one gets has two copies, right? One comes from your dad, one comes from the mom. For recessive disorder to occur, you have to have a bad copy of the gene both from the mom and the dad, one each. If you just have one copy that's abnormal or mutated as many people call it, you don't get the disease. So, in Friedreich's ataxia, the parents are going to be normal, but each of them is carrying an abnormal copy of this gene that we call frataxin. But some of the children are going to get the bad copy of frataxin both from the mom and the dad.
So, you have a double dose of it, then you get the disease. Because when you have that situation, the gene doesn't work enough to make the protein it's supposed to make. So, that's how the disorder originates, if you will. The majority of patients with Friedreich's ataxia start having trouble, predominantly balanced trouble when they are between about 8, 9, 10, 11 years of age, so right as they're becoming teenagers. There is a proportion maybe 15, 20% who don't get the disease until later on in their life after the age of 15 or 20 or 25 sometimes. There's a small number that have problems even under the age of eight, for example.
So, there's a wide range of age of onset, but the majority will have symptoms by the time they're about 10 plus minus one or two. One of the things we have realized is that if you look at the database we have, there's a bit of a delay in diagnosis usually about three to four years after symptom onset. We can talk more about it, because as treatments become available, we would like to shorten that time to diagnosis.

Dr. Peters:
What diagnostic tests are you using to evaluate for Friedreich's ataxia?

Dr. Subramony:
Right. Maybe I should paint a quick picture of how these children, particularly the children, get diagnosed.

Dr. Peters:
That's perfect.

Dr. Subramony:
Yeah. A lot of times the parents get worried because the child is a little bit clumsy, fidgety, doesn't seem to be able to keep up with their peers when they're seven or eight. They may be falling a bit more easily. A lot of times they end up in the pediatrician's clinic. Generally, at least this is my maybe not well-informed, but my guess that pediatricians like to be reassuring to parents. Also, this is a rare disease, so this is not in their radar. So, they talk about let's wait and see what happens. But if they see the child back in a few months, the child is clearly more stumbling. So, there is a decline and that should tip off the people there is something going on.
Typically, the patient may be referred to a neurologist like a pediatric neurologist. These children, a lot of times they have a foot deformity. They end up being referred on orthopedic surgeon because of the foot problem and a substantial number are picked up even during school exam as having scoliosis in their spine even before their onset of symptoms of Friedreich's ataxia. So, it takes a while for them to end up with pediatric neurologists. Pediatric neurologists are pretty skilled at making a diagnosis of Friedreich's ataxia. They find that the children have trouble with feeling things in their legs, particularly what we call physician sense. These children have poor ability to figure out where their joints are.
They often lose their reflexes when they tap them with a hammer and then they have abnormal nerve conduction, which is not a very pleasant test, but that's one thing we see. Occasionally though because of that, because the peripheral nerve is affected before the cerebellum, so both the cerebellum and the peripheral nerve are affected by this disease. Sometimes early on a little bit of a misdiagnosis happens. They think of this as a hereditary neuropathy for example.
There's a condition called Charcot-Marie-Tooth disease, CMT, and that's often a misdiagnosis for a short period of time before the pediatric neurologist stumble onto the idea that this is Friedreich's. But I would say that's not very common. Most pediatric neurologists can recognize and diagnose this disease. The one other thing is, of course, the ultimate confirmation of diagnosis comes from analyzing the gene for the Friedreich's mutation. Now the Friedreich's mutation is one of maybe 50 or 60... I cannot keep up with the numbers. ... growing list of conditions where the genetic mutation is called a repeat expansion. So, what that means is that these molecules that make up the DNA, they occur in a repeated fashion in many parts of our genes, even in normal people.
So, we all have, for example, the repeat that is involved in Friedreich's ataxia. It's called a GAA repeat in the gene, which is called frataxin. Normal people have fewer than, I believe, 44 repeats, but patients with Friedreich's ataxia will have much longer repeats, certainly usually about 66 or more in both copies most of the time. That causes the disease. The reason I bring that up is to detect this repeat expansion, you need a specific test that looks for the repeat expansion.
Many of the gene tests that are currently available, which are often commonly used in genetic conditions called sequencing tests, do not detect the Friedreich's mutation. So, there's sometimes a delay because a wrong test was asked for at the genetic level. So, there are few reasons why these children tend to have a little delayed diagnosis, but we would like to shorten that.

Dr. Peters:
Well, so once you diagnose a child or a teenager or whatever age, what are really the immediate priorities like now I need to manage this patient, I need to help them. What is the first thing you do?

Dr. Subramony:
Well, again, let's just talk about the 70, 80% that are children, teenagers, and then into their teens. They do have declining balance. Of course, one of the major help they need is with their motor abilities. As you know, there is no currently a medication that dramatically makes the motor abilities come back to normal, take it away completely, but we'll talk about the approved medication that seems to help the motor abilities in a minute. They may need appropriate rehabilitation, physical therapy, occupational therapy at that time and help with their schooling if need be like adaptive methodology in school, information to the education system about the handicaps these patients are facing.
Now, they are very smart. These kids don't have a learning problem, but they may need some help with their mortal problems and handwriting and things like that. We call it a multisystemic disease. So, the mutation certainly causes problems in other parts of the body. One of the key ones is the heart. So, there is what we call a cardiomyopathy. Unfortunately, physicians like to use obscure words for simple things. So, cardiomyopathy simply means trouble in the heart. We find that at this age, when it begins, probably 40, 50% may have an abnormal echocardiogram, which is a common test to be done. So, these patients require a cardiologist to see them on a regular basis because they can pick up these abnormalities.
Spinal deformity is often seen in this childhood age group in a substantial number of these children, and it causes pain. It probably adds to their balance problem a little bit because they have a scoliosis. So, orthopedists need to be involved in the care of these children and watch the spine. There are certain numbers on the spine x-ray. When they see that, they may want to say, "Maybe we correct it." A lot of times they may use a brace to prevent the scoliosis from getting worse. So, orthopedics and rehabilitation and cardiology care are very, very important.

Dr. Peters:
I completely agree with you that it sounds like it really takes an interprofessional multidisciplinary team to really take care of these great patients and to have them maximize their quality of life. Now, our Paralympian guest, Helen Kearney, she actually became an equestrian and won medals at the Paralympics. I think that's just so inspiring. Are there certain strategies like exercise and rehabilitation that you recommend for your patients?

Dr. Subramony:
Right. So, certainly, physical therapy and occupational therapy directed at the legs and the arms and maximizing function because PT and OT personnel are not like neurologists. They don't care what their reflexes look like. They're involved in function. How can we make the function better? So that's very important. Many places, maybe less so in the US, and it may be worthwhile pushing the physicians to get an... Occasional inpatient intensive rehab might improve function. The thing about physical therapy and occupational therapy is often they functionally improve for short period of time, but then it's going to decline and then you have to do it again.
At each point in time, you may have to expect some improvement. In general, we have come to recognize that aerobic activity, in addition to routine type of balance training, et cetera, is important. Aerobic exercise has probably a protective role for many aspects of your health, including your brain health. As you know, the AMA recommends 150 minutes of aerobic activity per week I guess for adults, but I guess most teenagers and over that age can try to perform aerobic activity like 30 minutes a day for five days a week or something like that. A lot of times, children and teenagers and youngsters with balance problem can do stationary bikes or swimming and things like that under supervision may be useful for that.
Coming back to your story about Ms. Kearney, we have another spokesperson that works with our patient group that just went on a trip to the Himalayas on a tricycle.

Dr. Peters:
Oh, wow.

Dr. Subramony:
He's about 40+, I think, with Friedreich's. Many Friedreich's people already know his name, but I won't say it, but probably it's on the website. So, people can do a lot of things with Friedreich's. With regard to exercise, I would say if you're seeing a cardiologist, let them know that you're going to do some aerobic activity and how much your heart rate can go up. Just make sure that they understand what you can do.

Dr. Peters:
Well, that sounds exciting. I mean the Himalayas, I can't even imagine. I don't know if I can do that right now. So, I appreciate the drive and the commitment of these patients. Now, there is some new exciting research in this area for patients with Friedreich's. Can you share with us the trials you've been involved with and really what is happening in the research arena?

Dr. Subramony:
Yeah, I think the research has been very exciting and I think one of the exciting things about these genetic diseases is once you know that this is the gene that's causing the disease, then you're able to trace what is happening in the system, in your cells, in your brain to bring about the disease from the gene to the disease. You can work it out fairly quickly. Of course, the gene was found about 30 years ago. So, 30 years is still quick in terms of medical developments. So, we know that this gene, the protein it makes called frataxin is deficient. It's not absent, but it's probably less than 30 to 20% of normal. We know that if you completely lose frataxin, you probably are not going to live. It's supposed to be not compatible with life.
But the frataxin works inside the cell, inside what we call mitochondria, and this is what I call the furnace of the cell where all the carbohydrates and fat you eat, that's where it gets burned. The frataxin has a role in making some key proteins and enzymes that handle the fat and the carbohydrate to make energy. So, we think that when you have deficiency of frataxin, your ability to generate energy from all the food you eat is actually reduced, and that's probably the reason why you get nerve cell loss and heart cell problems and so on and so forth to get the disease. At the same time, this problem in this metabolism within the mitochondria generates what we call oxidative stress. That's a word many people hear all the time.
The idea that the oxygen that you're using in your mitochondria, in your metabolism for very short periods of time can become toxic or harmful to your cells. Early work for treatment trials used what we call antioxidants. These are all around the place. Many of the nutrients on Amazon, for example, are antioxidants, coenzyme Q10, I mean vitamin E. So, we know of a lot of antioxidants. Some of these were tried, were not very helpful. We realized that the Friedreich's tissues do not defend themselves against oxidative stress. This recently approved drug, which is called omaveloxolone, in the laboratory was able to kickstart the defense mechanism of oxidative stress in Friedreich's cells. Basically, it pushes the cells to make molecules that fight against oxidative stress.
It was a nice feeling to see the first trial in Friedreich's to have a positive result where the results seem to keep up with what we predicted it'll do. So, it certainly seemed to have a slowing down effect. It is not something that will completely get rid of everything, but what we saw was that patients who are taking omaveloxolone in the trial, it was for 48 weeks, did perform better based on a neurological scale compared to the people who are not taking the drug. Then we did other kinds of analysis on the same data. We had followed these patients for four or five years in the trial, and we looked at the patients who got on the drug later on. After their placebo experience, they were put on the drug and also compared them with what we call a natural history dataset.
We have been collecting information on Friedreich's for a long period of time, what happens to the children on patients year by year, and we could compare them with that group. In all these analyses, patients who were treated with omav appeared to slow down a little bit compared to the placebo and non-treated patients. Over a period of year, they probably had a rescue that's worth about one year of progression that would happen naturally, so if that makes any sense. So, they did not decline by the amount that they would've declined over one year. That's what led to the approval of omav. I would say that there are more exciting things because the current research scenario is actually directed at the gene itself.

Dr. Peters:
Oh, interesting.

Dr. Subramony:
So how can we make more frataxin even when they have the mutation? Two studies are already phase one, early phase trials. One is actually to put the protein back by injecting under the skin, pretty much like insulin is given for diabetes, except to get the protein to the brain is a bit more difficult, a bit more complicated perhaps. We don't know. We are just beginning that study. So, this is the ability to take the normal frataxin and engineer it in some way, because if you just inject it, it's not going to get anywhere. But this is engineered in such a way that is able to get into various cells in the human body and be able to hopefully correct the frataxin deficiency. That's very exciting.
Very clever people in the laboratory also have designed synthetic molecules to the gene itself, to the DNA. Based on our understanding of how genes are regulated, these molecules are able to push the production of the frataxin gene to a higher level, even when they have the mutation. It's like brute force pushing it through the block that the gene has, if that makes sense. So, that also is an early trial. So, these are very exciting things because these will hopefully...
If they're able to bring the frataxin level back to about 50% and that's another interesting thing because the parents who are carriers have only 50% of frataxin compared to normal people, but they do okay. So, if you can get the frataxin up to half normal, you're going to be okay from what we can see. So, that's the aim of these drugs, to bring the frataxin up. You would think that if you're able to do that, it should have a tremendous effect on the disease.

Dr. Peters:
Well, you're giving us so much hope, and I just would have to say those children and those parents are so brave to go into those studies that are first in human, so that go from the mice into the human. So, I think that that's fantastic. For our Friedreich's patients, just getting to 50%, it's like crossing the finish line just to get to that 50% of that gene.

Dr. Subramony:
Yeah, I mean, I would also say having dealt with the families and patients, it's a tremendous group of patients and families and they fight for it. They're extraordinarily courageous and they come for studies. The Friedreich's Ataxia Research Alliance, which is the patient support group, has done a tremendous job of pulling people together and acting as a link between patients, families, clinicians, research groups, industry, and regulatory people. So, this whole work can move forward in a very concerted, orchestrated fashion.

Dr. Peters:
Well, Dr. Subramony, I think that you've just done so much to help this patient population and to be a champion for them. I just want to thank you and to thank our listeners. I look forward to more discussions in the future.

Dr. Subramony:
I appreciate your invitation. Thank you very much.

Dr. Peters:
Thank you.

Dr. Correa:
Thank you again for joining us today on the Brain and Life Podcast. Follow and subscribe to this podcast, so you don't miss our weekly episodes. You can also sign up to receive the Brain and Life Magazine for free at brainandlife.org. Don't forget about Brain & Life en EspaÃ±ol.

Dr. Peters:
Also, for each episode, you can find out how to connect with our team and our guests along with great resources in our show notes. We love it when we hear your ideas or questions. You can send these in an email to blpodcast@brainandlife.org and leave us a message at 612-928-6206.

Dr. Correa:
You can also find that information in our show notes, and you can follow Katy and me and the Brain and Life Magazine on many of your preferred social media channels. We are your hosts, Dr. Daniel Correa, connecting with you from New York City and online @neurodrcorrea.

Dr. Peters:
And Dr. Katy Peters joining you from Durham, North Carolina and online @katypetersmdphd.

Dr. Correa:
Most importantly, thank you and all of our community members that trust us with their health and everyone living with neurologic conditions.

Dr. Peters:
We hope together we can take steps to better brain health and each thrive with our own abilities every day.

Dr. Correa:
Before you start the next episode, we would appreciate if you could give us five stars and leave a review. This helps others find the Brain and Life Podcast. See you next week.

Paralympic Athlete Helen Kearney on Living Her Dreams with Friedreich’s Ataxia

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