There's a saying in medicine, when you hear hoof beatats, think horses, not zebras. Meaning, when you're diagnosing, think of common causes first. But of course, those hoof beatats could be a zebra, even if it's unlikely. That's why the zebra is the symbol for rare diseases. And some are very rare indeed, affecting only a few people. But the overall number is considerable. It's estimated that more than 400 million people around the world have a rare disease.

Historically, finding funding and treatments has been tough, but new DNA based gene therapies are offering hope. Could they be a gamecher? Then 10 years ago, a landmark study totally upended what we thought we knew about preventing peanut allergies.

It forced a complete reversal of guidelines at the time. And a decade later, we are now seeing the results.

DNA based gene therapies have the potential to revolutionize our understandings of rare diseases and offer new treatments. To learn more, I talked to University of Toronto researcher Rachel Harding about medical breakthroughs in Huntington's disease.

Then I spoke with Terry Purvalakis about his young son, Michael, one of an estimated 80 children around the world with a condition known as parapolgia type 50. Terry shares the story of how Michael's life was changed thanks to the first single patient gene therapy trial at Sick Kids Hospital in Toronto.

>> Rachel Terry, welcome to the rundown. How are you doing?

>> Great. Thank you for having us.

>> Yeah, thank you for having us. This is awesome. Yeah, no worries. Rachel, let's start with you. Walk us through the recent Huntington's disease gene therapy. Specifically, what does 75% slower disease progression actually mean?

>> Yeah. So, maybe let's start with what Huntington's disease is. So, this is a rare inherited neurodeenerative disease characterized by progressive, which means symptoms that get worse and worse over time, which are motor, so movement, thinking um and psychiatric symptoms as well. And everyone who has Huntington's disease makes a slightly different version of a protein called the Huntington protein.

>> Okay?

>> And so the gene therapy that was designed by this company Uniure is delivered by brain surgery. Um and it's uh genetic instructions that are packaged into this harmless virus um that spreads through the brain and tells the brain to make less of this kind of harmful form of the Huntington protein.

And so there's been a whole bunch of folks who've been in this clinical trial for quite a long time now and we just got some data a few months ago now um which seems to suggest that there was slowing of symptom progression by about 75%. And so this is equated to symptoms that would normally progress um in their aggressiveness in the course of a year that would now take four years.

>> Okay.

>> So this is really exciting. This is the first time any company has shared a date any data that seems to suggest that they're able to slow down the course of the disease. We do have to be a little bit careful though because this is a very small trial.

>> So say how many people?

>> 12 people. Okay.

>> So which is because we don't want to give brain surgery gene therapies to hundreds of people at once until we're really sure you know are they safe? How well might they be working? We need to get some good signals from those first. Um and so we've just got 12 people. And the other problem with these kind of trials is it's not always practical or ethical to do um a placebo arm.

So actually what they're doing is they're looking at what they call a natural history cohort. This is where they track data from people who have Huntington's disease u but they're not in the trial and we're trying to see how they would progress without the drug and then making that comparison. Um and so there's a bit of a debate about how good that is as a comparator. Um, but nonetheless, it's still an encouraging step forward. And I always like to think about these super brave people who took this gene therapy, had this brain surgery before they knew there was any possibility this might be definitely okay, and they've been walking around for the last few years with this gene therapy in their brain, lowering the amount of this toxic protein, and how amazing that is.

>> Rachel, what would you say was the key breakthrough uh that allowed sort of these incredible results that we're seeing? Yeah, I would I always bring it back to the patient community.

The Huntington's community themselves are one of the most hypervigilant and organized communities most well read up on everything to do with their disease, how to organize and how to um best be involved with clinical trials. So their engagement with natural history studies all those I think it's over 10,000 people who signed up for every year they go and they get certain measurements made and if they these people hadn't done that we wouldn't have been able to do this trial and to make this comparison.

I think that's a really amazing thing and it's not just the folks who have Huntington's disease it's all their carers their partners who drive them to these appointments but their clinical neurologist um that is what has really enabled things for this community in my opinion

>> Terry you know all about this type of struggle. Your son doesn't have Huntington's disease, but can you tell us a little about uh your son's journey?

>> Yeah, Michael had SP has SPG 50 or parapollegia type 50. We were told go home and love him. He'll be paralyzed from the waist down by the age of 10, quadripollegic by the age of 20. He'll never walk. He never talk. We went home and lost our minds that evening.

>> I locked myself in a room. 24 hours later, we realized that we could do something that gene therapies and ASOs or antisotides. there was therapies that could be done. And uh a month and a half later, I flew around the world. I met all the experts in gene therapy. We hired a team out of Dallas, Texas, and we started doing this therapy for Michael.

This uh they call it a proof of concept. Prove that you can create a therapy. Um about a year later, we showed that it would work. It was working in mice and it was working in cells. And we had to raise $4.5 million. At that point, um our community in Toronto came together. We raised $4.5 million over four years. and we were able to safety test the drug, make the therapy, and treat Michael in March of 2022.

>> We have some photos of Michael that I want our viewers to see. How is Michael doing today? When was this uh this photo taken?

>> This photo was taken uh well before his therapy. He had a major seizure that lasted about 3 hours.

>> Wow.

>> And they didn't think he was going to survive. And this is him waking up from that crazy seizure.

>> And we have some photos here as well.

>> Yeah, that was uh when Michael was um 12 months of age when they diagnosed him with this disorder. Uh well they they didn't exactly know what it was but they diagnosed him with microphille. We went to Greece for a pilgrimage um to try to pray away the disease and um yeah and this was just

>> this is him. He's a happy little kid. You know

>> how is he today? Is this

>> Yeah, he's good. You know he's um Michael was the most severe child in the in the in the disorder. Um but he's able to communicate with us, tell us what he wants. Um he hugs and kisses us. He shows affection. um he's able to stand, you know, he's improving. Uh but he was the most severe. There's a spectrum of disorder. Right.

>> Right.

>> And um so he he probably will never walk. Um we hope that he'll talk someday, but if he's able to tell us that he's in pain or he wants his diaper changed or if he wants to go to bed, then when we're gone from this earth, we'll have we'll have a one.

>> Yeah.

>> Rachel, what do these results tell us about the current state of disease fighting medical research? I think we're in a really exciting phase of drug discovery and finding um treatments for diseases which have often been overlooked because they're not seen as commercially viable by really large pharmaceutical companies.

Now we have technologies that allow us to almost copy paste for different types of disease and to create therapeutics hopefully for many many people. That's such an exciting place to be in our society.

>> Um now there's a lot of excitement in gene editing tools. We've heard uh technologies like crisper, CRI, SPR, but in terms of this Huntington's treatment, it did not involve that. Uh tell us a little bit about the technology. You touched on a little bit, but tell us a little bit about the technology.

>> Yeah, so um this therapy is delivered like many other uh gene therapies through this harmless virus. Um the drug itself is called AMT130. The virus packages the instructions for something called a microRNA.

This sticks onto the Huntington message molecule. This is kind of the in between of our DNA genetic instructions and the proteins that they encode. And we have these message molecules that kind of are the in between of those so that we can faithfully copy the DNA and turn it into protein. Um, and so this microRNA sticks on to that message and then stops the protein being made. Um, and so that's the technology. And so you can imagine that, you know, now we know how to do this for different diseases. we might find another disease where we want to switch off another gene or turn down the levels of another protein.

>> Terry, even when the science is promising for diseases like this, there are obviously some real barriers. You tal you mentioned a number there, four four million. Uh that's just one side of the [clears throat] conversation there, but tell us a little bit about the barriers that uh that families are facing when it comes to these diagnosis.

>> Yeah, I mean it we're not meant to create therapies. A family is not meant to raise $4.5 million, do toxicology in animals, find a manufacturer. This is not something we should be doing. And that's the barrier that we have is that because they're not commercially viable, um that you know companies are not going to spend a billion dollars to make a therapy like this, there's no interest.

And that's why when I had to quit my job and start a pharmaceutical company or

>> no medical background, correct?

>> No medical background at all. Um well, I had smart people around me. So, you know, it was a team effort. It wasn't just me. was hundreds of individuals and now I have a team of people that are much smarter than I am um to get these programs to the clinic, show that they work and then move them towards approval because the reality is if we treat a children, we've really done a disservice for the community because there'll be children born every day. There'll be hundreds of over the next 20 years there'll be thousands of children and they could have been treated with this therapy and they will not have unless we got it approved.

>> Can you help us understand how rare these diseases are? like Michael's condition, how many people in the world have it?

>> So, Michael, Michael's one of 130 in the world. He's the only child in Canada. Um, if you look, put in perspective, there's 10,000 rare diseases. 5% of them have a therapy of any sort and 400 million people in the world have a rare disease. One in 10 of us will be affected. So, someone that you love, you know, will have a rare disease. Parkinson's, ALS, um Alzheimer's, anemia, hemophilia, someone you know has a rare disease or will have a rare disease.

>> When you were starting your family, you I imagine you didn't think that this was what the fight that you were going to be fighting, that you were going to be an advocate for treating rare diseases. What other changes are needed uh to be successful in this fight?

>> Uh from an individual perspective when you're in this?

>> Yeah.

>> Uh well, I was an introvert. It doesn't show it anymore. But once you do a 100 interviews, you know, it kind of breaks you afterwards. Um, but you have to have a strong will. Um, you know, we were when we first put out our story, people were telling us to put down Michael that he's, you know, that he doesn't deserve to live and you have to have a strong backbone. You have to have a strong will. Um, you have to have a never give up attitude and you have to have a a support community around you. And luckily, I have an amazing wife and amazing children that supported us. um an amazing community that came on and said, "We are not going to let Michael's um have this disorder. We're going to be here for you." And then we were fortunate enough to meet amazing people along the journey to help us do what we needed to do to get there. It was again, it's not meant for families to do this.

>> I I have to imagine that you get emails, phone calls, messages from families who were in a similar situation uh than you were.

>> I get 15 calls a week. I had two just on the way here. Um it's non-stop because families are trying to save their children. They see my story and they want to do what I did and some of them are successful, some of them are not. Um, and it's something that we have to figure out. We have to figure out a path forward. Thankfully, technology is changing rapidly. Uh, what we thought was non-curable 10 years ago is curable now. And if our children were born 5 years from now, it'd be a different story. We'd have probably therapies right off the bat.

Some things we need to do are uh newborn screening. We need to have genetic screening for every single child that's born. That way when a drug is in the clinic, we can treat a five-month-old, a two-week old, a one one month old. And those children will be more towards a cure than a treatment. Because as you can imagine, it's like a sliding scale. If we catch them early enough,

>> it'll be more towards a cure. If we treat them at 17, it's less and less of a cure, more and less and less of a treatment even, right?

>> So that's where we have to really step up and government has to start really investing in this um new technologies and new innovations.

>> Rachel, Terry had mentioned a path forward. So I am curious how can the the lessons learned in the Huntington's case apply to the way we treat genetic diseases in general.

>> Yeah. Well, I think doing any of exactly the work that Terry discusses like this is hard and it's quite difficult. Uh we need a community to mobilize both scientists and government to allow us to find new paths for how can we get drugs from [clears throat] ideas that scientists have in the lab to things that we can test and develop in the clinic to into the most important part of this is getting the drugs to the patients.

And one of the biggest barriers that we can kind of foresee with gene therapies in particular is the barriers for how you actually run the clinical trials, how you actually get approval, and then how expensive those drugs are at the end. Typically, we're talking in the order of maybe$1 to5 million per patient. Um, and how Health Canada and other approval agencies are going to oversee administer that and ensure that people can actually be treated with drugs that are maybe already available. um but they're just so expensive. So that's going to be a problem we've got to figure out.

>> What kind of diseases uh might be in line? Uh next.

>> Yeah, it's a great question. I think um I really like that Terry brought up this statistic that one in 10 people in the world have a rare disease. And so these are all kinds of different things. Some of them we really don't understand. We don't really know if they have a genetic basis or if it's some other environmental factors or something else altogether. Um, but I think at least those with a a defined genetic basis, there's a very obvious path forward for how we can use some of these emerging technologies with gene silencing or crisper, other kinds of editing technologies to try and find viable therapeutics and I think that's where things are looking really exciting in the next 5 to 10 years.

>> All right, my last question to both of you. Uh, Terry, I'll start you. What's your one hope for the future of genetic medicine in the next say 5 to 10 years?

>> My hope is that um the technologies evolved to a certain point where a child is born, we we do a genetic screen within a day and on day two they're getting treated

>> and I think we're not far from that. I think in the next 5 or 10 years that will be we'll be eradicating disorders.

>> Um and that's why I say Michael was just born a bit too early. You know, if he was born 5 years from now, um he would have been cured. Unfortunately, he was born now. Um and we have to do what we can. But that's our hope is that that we eradicate these these disorders so that our loved ones will never suffer from these diseases.

>> Rachel, you get the last word.

>> Okay. I think something that's really exciting with these technologies is the underlying science didn't even exist maybe 10, 15 years ago. And so it makes me so hopeful about what is currently in the lab. Like what scientists at University of Toronto and other places around the world, what they're developing and what possibilities they offer for the future. Um, I don't think we even know what technologies will exist that could enter the clinic in the next 5 to 10 years. And that's really exciting.

>> Very exciting times. Rachel, I'm going to we're going to leave it there. Thank you so much for your insights. Terry, thank you so much and wish your family all the best.

>> Thank you so much. Really appreciate it.

>> Thank you.

>> Peanut allergies are common and can be deadly. For years, parents were told to avoid feeding them to their kids under three. But in 2015, that all changed. Research found that introducing peanuts as one of a baby's first foods actually cut the risk of developing food allergies.

A study published in the journal Pediatrics this October says this updated guidance has had a big impact. I asked Josh Koig, assistant professor in the department of medicine at McMaster University about what the research shows and what it means for people who suffer from food allergies.

>> Josh, great to have you. How are you doing? doing very well, thanks. Thanks for having me on.

doing very well, thanks. Thanks for having me on.

>> Of course. As someone who researches food allergies, how groundbreaking is it that we are seeing peanut allergies plummeting in children?

>> Um, I think it's a very promising sign. Uh, as you know, the recommendation shifted to uh from basically avoiding allergens early on in life to early introduction and early feeding at about 4 to 6 months of age. Um, and this happened around 2017, which is the first recommendation. And in 2021, there was a more expansive guideline and you know this is based on a large study called the LEAP trial uh where they found that early introduction had a massive impact on becoming allergic to peanut very particularly.

And I guess now is probably just around the time that we would be able to see the beginnings of that signal that you know we really are impacting the incidence of this uh of the disease. Um, and you know, I won't say that the the data are um, you know, as you know, there's like an 81% decrease in sensitization in a leap trial. That's not what we're seeing yet. But the difficulty is, you know, that's a very controlled environment. And in the real world when, you know, you're in clinics and there's clinics all across the country in the US, which is where this research was done, uh, you know, uptake by patients, these are all questions that are are, uh, you know, still open. But it's a really positive sign that we are for the first time I think in modern history seeing a decrease in the rate of peanut allergy.

>> In layman terms, can you help us break down the science here? Why does introducing peanuts and peanut products uh like peanut butter um lead to a drop in in allergies?

>> So for you know 98 to 99% of us peanut isn't a problem. Um it's only in a a much smaller fraction 1 to 2% where people become allergic. What typically happens when we eat a food is we become what we call tolerant to it. Our immune system works in tandem with our intestine to say, you know, those foods are okay. We need to take those things in to get nutrients from them. So, we don't want to have a bad reaction.

But in 1 to 2% of people, uh that doesn't happen. Instead, they mount an immune response against the allergen. And then that immune response can have, you know, the effects of an allergic reaction uh when they see the allergen again. So what we think is going on is that by providing the allergen early on at that 4 to 6 month time point you're introducing allergen in a controlled way in a controlled environment such that the immune system hasn't had time to accidentally be exposed to the allergen in a negative way that would make you allergic. So essentially we're just taking advantage of what we know about how the immune system works and and using that to tolerize people before they have the opportunity to become allergic.

I can imagine there are people who are looking at this study and are quite excited. They may not be um allergic to peanut products but they might be allergic to something else and I am curious is it recommended that uh we try other allergens like uh tree nuts or eggs.

So I'm not a clinician so I can't provide clinical recommendations but I can say that uh you know in speaking with my clinical colleagues there are actually schedules that are recommended for early introduction of essentially all foods because they think that that really is the way that we are going to you know decrease the incidence of new peanut allergies. But as clearly evident by this study you know it wasn't an 81% decrease that we saw you know in these patients. It was it was much less than that. Um and people are still becoming allergic. So, you know, I think that yeah, you know, following those schedules is a really important piece of this, but another important thing is that people are still allergic and are becoming allergic and we do need to find ways to deal with those people as well.

>> So, I want to clarify. So, people can still be allergic to peanut products or other products even if they've had them at at a young age.

>> So, um you ask a very good question. I suppose we don't know exactly the answer to that question. What tends to happen is that people on that first introduction to the food, their child have a reaction right away and then they end up having to go to hospital and then they end up being diagnosed. So essentially the thought process there is that they've already become allergic before the early introduction.

>> Peanut allergies has been getting a lot of headlines not only uh from this study uh and you had mentioned the US. I actually want to to uh pull a clip. Uh this is from Robert F. Kennedy Jr. who is as we know the US Secretary of Health and Human Services. He gave an interview recently uh talking about peanut allergies and exposing infants uh to peanut products. Let's have a listen to that.

To me that is not a convincing hypothesis because number one in my own personal uh experience was my house was was so filled with peanut butter and I was eating peanut butter two meals a day and my wife when she was pregnant was eating peanut butter and the kids were given peanut butter from as soon as they could chew food and yet we still had peanut allergies in our house. We need to look at um aluminum adgivants and vaccines um which fit the timeline perfectly. The increase of aluminum and the is is in lock step which began in 1989 which is in lock step with the expansion of allergies.

>> As a researcher I have to ask what is your response uh listening to that video?

Um well, you know, on the one hand, anecdotal, um you know, it's really unfortunate that uh uh Mr. Kennedy's uh children have peanut allergies. Um but, you know, this study involved tens of thousands of people. So, this is an agg, you know, much larger aggregate than than an anecdotal study. um you know there really isn't any evidence that would support the notion that alum or aluminium in uh uh vaccines is associated with allergy at all.

In fact, you know, there's been multiple what we call systematic reviews which essentially looking at many different studies that have tried to look at this and essentially there's no connection between vaccination and becoming allergic as far as we can see. Um, and uh, I suppose I have a small issue with the timeline there because I'm pretty sure that alum was first introduced in like the 1930s and has been in vaccines for the better part of 70 years or something like that. And, you know, the prevalence increases that he's talking about generally are from the 1990s onward. So, I I'm I'm not really I I I'm not sure I buy that as a as an explanation.

You know, we really don't know why the prevalence of allergy has been on the rise. Um and I think that that's a major issue and and you know I don't think I you know in contrast to what Dr. sorry Mr. Kennedy is saying there I think um you know there are many fantastic researchers that are trying to figure this out. They're trying to figure out what was been causing the increase in these allergic diseases and you know really consensus hasn't come about on that but I really I don't see any evidence that it would be anything related to vaccination. In fact, the opposite. I would say studies are kind of suggesting that, you know, for example, if you get a vaccine, you're less likely to have eczema.

>> Well, I want to pick up on that in terms of the research that's being done. Are we any closer to identifying the what, like what causes food allergies?

>> Uh, well, you know, unfortunately, not really. Um, you know, again, not for a lack of trying. The difficulty with this is people become allergic, very very early. So, think about how we could know this piece of information. Most times we know that someone's allergic when they've eaten an allergen, had a bad reaction and gone to hospital. So trying to figure out what happened before that is difficult because we don't know of the you know out of a hundred people maybe one or two might become allergic to peanut right um and it's been very difficult for us to pin those down.

and the things that we have found that have made some associations for example like peanut oils in baby oil uh those things resulted in changes so you won't find peanut oil in baby oil anymore because of the possibility that you might be sensitized and researchers found that out and we enacted changes to you know avoid that potential issue so um I think these large epidemiological studies are likely to reveal new things in the future. But for right now, I I think the bigger issue is how can we engage in prevention and then how can we engage when people are allergic to basically stop them from being allergic and give them the opportunity to live a regular life.

>> All right, I want to change gears a little bit. I want to talk about we're in an age of of disinformation and misinformation particularly when we talk about uh healthcare. Um, and I want to talk about a a Facebook post uh that claimed there was a vaccine for peanut allergies. And I have to imagine that you and your colleagues who are deep in this research in allergies would probably be one of the first people to know that this was in the works. And so, uh, this was not the case. Of course, you and several of your colleagues at McMaster put out a statement to say it wasn't true. But people are are curious. Is there a vaccine in the works for peanut allergies?

Um, so yeah, I mean I think that that was an unfortunate situation of AI hallucinating uh based on on some potentially truthful information and then uh a lot of essentially gibberish. Um, you know, we are uh engaged in in multiple studies testing potential therapeutics uh in food allergy and you know trying to figure out what what options are available and what's going to be effective.

you know, early in development. We do have some, uh, studies looking at what would essentially be vaccines. Um, but, you know, they're nowhere near the point where we're giving them to humans and seeing an impact in the human. And, you know, it's very unfortunate because I I would absolutely love to say to everyone here, you know, I have the solution. Um, I don't, but I can tell you I don't sleep very much because I'm on the case and I'm always trying. I'm always working towards it and so are all of my colleagues. So we're we're working really hard towards this and uh you know we have multiple lines of inquiry to try and do this as well as trying to figure out you know what causes allergy, what makes allergy persistent in people and we're hoping through those research programs we'll be able to find good interventions that will have an impact on people.

>> Well let's stick on that point about sort of battling the misinformation disinformation as as a researcher. Uh how is that battle? What do you do?

It's a really fantastic question and you know I think engagements like these are are good opportunities. I you know I definitely know that my colleagues and I were you know overwhelmed by the amount of work that we have to do both within the research program and then beyond. So you know the notion of uh doing engagement is is is we don't do it as much as we would like to. So I think one piece that we need to do is engage more with the community and and you know when I engage with community members which we do quite a bit through Food Allergy Canada which is a partner organization a fantastic partner organization um you know I I find that people tend to go oh okay well now here's a face to a name.

but the difficulty is that the disinformation process is so fast and it's really hard for us to you know cut off everything that comes out and and you know make statements about everything when the statements are you know very clearly false and very clearly about us. It's a little easier like in this disinformation campaign uh or this disinformation AI post situation, but um you know I I think that this is an open question. How do we as researchers demonstrate what we're doing to try and impact this problem and and you know get the trust of the general community back?

>> Josh, really appreciate. Thank you so much for your insights and your research. This is really exciting stuff. Thank you so much.

>> Thanks so much for having me. [music]

Today is Giving Tuesday and we're asking you to help us support media literacy and keeping Ontarians informed. Donate before midnight tonight at tvo.org/giving Tuesday and every gift will be matched up to $250,000. Donate $100 or more and you'll get your very own limited edition retro TBO toque. Your support builds a stronger, more informed Ontario. Until then, we'll see you tomorrow.