Do you believe in destiny?

Well, this is a story of destiny.

We were ready to lose everything.

We were not ready to lose her.

This is what dreams are made of, being able to treat these diseases and giving hope to the patients.

That's all you can ever hope for, and we are so blessed to be able to be doing that.

At Auburn, we work hard to develop research that will help save lives and change our world for the better.

And in our College of Veterinary Medicine, scientists have been working for years to develop a treatment to improve and extend lives of cats affected by a genetic disorder that progressively destroys nerve cells in the brain and spinal cord.

Auburn University established a partnership with the University of Massachusetts Medical School 15 years ago to move the research into helping children suffering from the same progressive and fatal disorder.

Human clinical trials are now underway at the National Institutes of Health in Maryland, and this collaboration, which involved combining animal and human medicine studies to treat rare diseases that affect both animals and humans, could quite possibly have life changing impact Porter was our first son, our only child.

He was born in September.

2012.

We had a normal pregnancy.

He was the first grandchild for both sets of our parents, which was a special thing for us, and of course, being a boy.

Michael had a lot of things that he was hoping to be able to teach Porter about hunting or about sports and all of those fun things.

But probably at like three months, I'd say.

I started noticing that Porter had a little bit of a twitch in his eye, kind of just, his eye would bounce back and forth.

And I had mentioned it to Michael and, you know, you would see it every now and then.

We didn't really feel like anything was severely wrong, but at our church, our Sunday school teacher happened to be our pediatrician, Dr. David Smalley.

And so we said, Well, at his four month checkup, I'm just going to say something to David just because I just want to use my mind a little bit.

So I did.

So I showed him and he said, Well, let's just watch it.

He seems to be checking all the other boxes and, you know, progressing normally.

Let's just watch it and see.

So, David, being our Sunday school teacher, I think he probably went home and thought a little bit more about it and said, well, let me just let's make an appointment with an ophthalmologist in Birmingham.

He's a really good friend of mine.

Why don't you just go see him and let's just make sure that we don't have any vision issues.

Yeah.

So it was probably within a week of visiting Dr. Smalley.

He had already scheduled an appointment at the doctor in Birmingham and we took Porter up there during the week on, you know, mid-morning or so, 10:00 in the morning.

And the doctor, everything seemed normal but had he dilated Porter's eyes, we wait a few minutes and he came back and he looked in the porter's eyes and, you know, like, you could just you could tell, like, his demeanor and everything changed, like.

Like he knew something was serious, or something was going on, and it was like, it's almost like he you know, he's trying to figure out, how do I say this?

Whatever.

And he actually left the room without really telling us anything at that point.

And Porter was four months old.

So he's so small, you know, and you just you sit there and you're like, oh, my goodness, what's happening in your mind just starts to race like a hundred miles and hour.

But with him being, he was four months old and everything else, we thought at that point was was normal except for his eye twitch really I mean, he may have had somehow like some slight little bit of delays and, you know, learning or something.

But we, you know, first child, we didn't acknowledge or recognize that there was anything going on at that point.

So we thought, you know, the worst possible scenario's like, well, he can't see well, the doctor came back in within a few minutes and and basically said I've I've made an appointment you know at UAB at the geneticists like you need to go there now and have basically have blood drawn and do a urine sample.

And that's why we went straight to the geneticist.

Yeah.

Dr. Bess Cortez was her name.

And so she kind of of course, physically examined him that day.

Everything physically looks fine.

We did.

She said, okay, well, typically this is a sign of 15 different genetic disorders.

And she said, we're not going to know exactly what it is or it could be nothing.

What we have to do, since he's so small, we can only test for three of them at a time.

She said, we're going to test for three At first, we'll know one week if any of those are positive.

If it's not one of those three, you'll have to come back and we'll test for three more.

So we said, Okay.

And she said, We're going to test for Gangliosidosis, Tay-Sachs disease and Sandhoff disease, those were the three.

It was about a week after we were at the geneticists and the eye doctor and everything.

We got a call from the the genetic counselor that worked at UAB and called Sarah and gave her the diagnosis of GM1 Gangliosidosis.

Yep.

And so we were both at work at the time, and Porter was at daycare and so I got the diagnosis and Michael, called Michael immediately told him that this is what he has.

And so he looked it up online and said that, you know, Porter, it says that the life expectancy is about two years.

We went up there the next day immediately because they asked us to come up there and the only thing I remember was that we left there and she gave us a printed out piece of paper that kind of told us what the diagnosis meant, which meant that hopefully Porter would live to be two years old.

And these are kind of the things that could happen.

Just please take your son home and take care of him.

And you're like, we there's there's nothing that we can do.

There's no treatment.

There's no medicine that we could take.

And she basically said that it's better to be proactive as far as doing physical therapy, proactive as far as needing potentially a feeding tube and all these things.

And we said, okay, but there's there's no clinical trial for some type of drug that we might could be in.

And she said, No, there's nothing.

And so she we walked out of there with a piece of paper The research came about by the discovery of cats with these diseases, by Henry Baker and his wife in the early 1970s.

Well, it didn't start at Auburn.

It started really started at University of Alabama at Birmingham My mentor and colleague, Russell Lindsey and I started a department called Comparative Medicine I got a call from a veterinarian who graduated a year after I did and he had an interesting case of a cat that had been seen by several veterinarians in the Birmingham area and diagnosed with everything from a fracture to a an infectious disease.

And my veterinary friend Rick Becker said you know, this doesn't fit any of those.

So he called me and it was had tremors and difficult standing eating and I had seen a lot of cats at my internship in Boston.

Rick had seen a lot of cats and we were stumped, we didn't know what it was.

And that cat was owned by the disc jockey Brennan.

And it was a different era when teenagers listened to music on the radio and and this disc jockey from Birmingham was the person that all these youngsters listened to.

Well, one of the teenagers who was a fan of his bred amateur breeders of Siamese Cat.

So this was twin daughters, and they gave Brennan a cat as a gift.

So I had a theory.

I knew this cat had a strange viral disease.

And so I got the neurologist and the virologist, pediatric virologist.

Everybody I thought could help us understand this disease to advise me about what tissues they needed.

And so we did a complete necropsy and we took every sample we could think of And Russell Lindsay was a veterinary pathologist in addition to being a lab animals specialist.

So I gave Russell the slides from this cat's brain.

He called me he said, Henry, you need to look at this, cause your cat has a storage disease.

My goodness.

Russell, that's wonderful.

I had no clue what a storage disease was.

Particularly for my research.

I look at GM1 and GM2.

Gangliosidosis but your lysosomal storage diseases And if you don't know what that is, those are genetic diseases.

That cause are caused by a lack of an enzyme that breaks down a lipid substrate in cells, and they continue to accumulate.

And you can imagine, like, if you didn't take the trash out in your house, ever, you would have to leave.

Same thing happens with our cells of cells degrading because there's too much byproduct in their if your body uses enzymes to digest food, it's the same kind of thing, except these enzymes are in the brain.

And so an enzyme deficiency in the brain causes nervous system dysfunction.

Children develop normally for six to eight months, and then they start to miss developmental milestones and their parents realize that they're not developing normally.

From that point, it takes another six to eight months to get a diagnosis.

And unfortunately, in most cases, these diseases are so severe that by the time diagnosis is made, it's too late to do much to help these kids.

And eventually the neurons start to die and the children eventually die as well.

So this class of diseases was first described in 1881 by a guy named Warren Tay.

And that's where the name Tay-Sachs comes from.

It's been 135 years that we've known about these diseases.

And still there is no approved treatment The disease progression usually takes place over four years or so.

Kids die by four to five years of age.

So Russell decided he would give the slides to the medical neuropathologist Ricardo Ceballos, who was a Spaniard.

Really interesting guy.

And so he wanted Ricardo to confirm his diagnosis that it was a storage disease.

The week, the very week that Ricardo reviewed those slides, he had a visitor name was Dr. McCann.

Dr. McCann was on the faculty at Johns Hopkins School of Medicine.

His specialty was the diagnosis of inherited disease.

When Ricardo showed him this, these sides of the brain, they almost fell out of their chair because it was, McCann told me he thought Ricardo was playing games.

He thought this was a child with Tay-Sachs He did not believe it was a cat.

Week later, he said, you have the first biochemically confirmed case of GM1 Gangliosidosis in a cat.

The one of the interesting parts about that was that we knew we had something important in terms of a disease that affects humans and animals.

And they were identical, pathologically identical but we had nothing if we couldn't reproduce it.

It was an inherited disease.

We had to have information about how this cat disease, we knew how the disease was inherited in people we didn't know how it was inherited in cats.

And that's where the the mystery started because Mr. Brennan and his family had no idea of the names of those twin girls who had a cat So it was left to me, encouraged by Russell, left to me to search for the family.

And it took a lot of work over a month.

And the twin girls were, of course, crazy about these Siamese cats.

And the mother and son Cat had many, many litters.

And so these girls would give their cats away.

We started picking up cats that were siblings to the affected cat.

So my wife and son and I started a little group of cats.

When I moved to Auburn, Tom Vaughan the dean at the time invited me to become director of the Scott Ritchey Research Center.

So I brought the colony with me.

The Scott Ritchey Research Center is a very unique resource it's there's nothing really like it in the United States.

It's a and endowed program that was established by two major donors and then a lot of private contributors afterward to study diseases of companion animals.

And the leadership of the Scott Ritchey Research Center has transitioned very well from one person to the next.

And so we think about Dr. Henry Baker and his leadership of the center and the transition from him to Dr. Nancy Cox, and then from Nancy Cox, then to Doug Martin.

And there's never really too much lost in those transitions because they work together so well before they ever assume the directorship role.

And we've just been very fortunate to be able to have this succession of leadership that allows there to be continuity.

And that continuity allows us to make progress in focusing on very specific diseases and advancing the knowledge that allows us to come up with cures.

The College of Veterinary Medicine has a very broad mission, and it focuses principally on diseases of animals and how to improve animal health.

But we also know that animals are critical to the health of people, and it may be as a pet, it may be as an agricultural animal.

It may be through understanding of biology and then applying our understanding of animal biology to human beings.

And so GM1 gangliosidosisis one example of that.

Approximately one in every 100,000 live births is affected with Tay-Sachs disease or GM1.

The the impetus for all of our effort at Scott Ritchey has been a little fellow named Porter Heatherly.

We had tried to find a church for a couple of years, and whenever we moved to Auburn and we decided to go to AUMC because we just kind of felt like that's where we needed to be.

Went to a couple of other ones and we just decided to go there and we decided to start going to the 8:00 service.

And we always used to wave at this gentleman that wore his tennis shoes with his khaki pants and a sport coat, I always used to wave at him, and he was there every Sunday, nice just kind of friendly wave.

And so I remember what what kind of connected us was Michael.

We were reaching out to figure out kind of get our feet under us of what this meant.

I had found the national Tay-Sachs and Allied Disease Association and basically just joined.

And it's just it was a way to connect with other families.

And they had an annual conference just to kind of communicate with people that had it was, you know, GM1 and Tay-Sachs and several other diseases.

We got the first newsletter that we received from them.

It had our name, basically name and address listed on there as it was in the wrong state, Arkansas or something like that.

Yeah, just this had the wrong address, basically.

So I called to correct them and told to our correct address.

And at the time we lived in Opelika but I guess just saying that we were in Alabama, she said, Well, do you know that there's research at Auburn University, you know, regarding GM1 and so I was like no we don't we have no idea that this is a month after our diagnosis.

And so the first thing I did was just Google, you know, Auburn University GM1 research or something.

Well, the first page pops up and it's Dr. Doug Martin.

And I called Sarah immediately and I was like, You're not going to believe... you remember that guy from church that you wave at, that wears those tennis shoes.

And I said yeah.

And you're like, you're not going to believe this, Sarah.

That's who is heading up the research at Auburn University.

And we were like, I mean, just floored We really struggled, you know, with Porter's diagnosis for for a little while.

Just like, you know, was this happening to us?

This is our first child you know, like, you just you can't prepare yourself for a terminal diagnosis for your child at any point, I don't think.

But just learning that and making that connection like it gave us, like so much hope and so much to look forward to of like what can we do to help or what do you know that you can help us with and what have you seen in, you know, what you've researched and kind of you know, I always say this kind of analogy.

You know, you always are, let's say your life's direction is headed in one way.

And so certain things happen and you might detour off and go to the right for a little bit or detour off and go to the left.

And we were just struggling to even find a way to get back going straight.

And I feel like whenever we saw that and realized that that was just right down the road, I think that for us, I said well I'm going to call him I said I'm going to call him.

So I just the number on the website, I called and left him a message.

And I even I think I remember my message was like, I'm sorry, this is going to be the most random phone call you probably ever received and told him that we had just been diagnosed.

And he called back and he said, well, we would love for Porter to come up here.

We would love to meet him.

A lot of the people who have been working on this have never met a child that has been diagnosed with the disease.

So I think that that would be great for them to meet him.

And of course, we had to decide as a family if that was something that we wanted to put out, there would be like, okay, or are we willing to share our story and share what potentially will happen in the future with everybody?

But we knew I mean, that was never really a question.

It was just more like, all right, we're ready.

Like this is what we need to do.

And we were willing to share his story with everybody and wanted to do everything we could.

We knew that the research was not the point where, like, it was going to help or like he needed it immediately.

He needed treatment immediately.

Like we realized that that it wasn't going to help him, but it still gave us like so much just hope and determination of why we're going to make the best of his life and figure out what we can do to promote this research and get people to donate money and move it forward.

So, you know, the ultimate, you know, goal and hope for us is like somebody like us gets an early diagnosis and goes to the geneticists and they say, here's, here's is what you need to do.

This is where you need to go.

Who you need to see and there's a cure or there's a treatment or something that would help alleviate some of the symptoms.

I mean, we really went for over a year, I would say, without really having any major issues and once we had about 14 months, we had our first seizure at 14 months.

We didn't realize it, but he was having trouble.

Like when he's feeding on the bottle, he was aspirating so he's getting fluid into his lungs and got pneumonia and ran a fever.

And the, the fever triggered seizures.

And so he actually had seizures at our house and we got him to the hospital, the emergency room in East Alabama.

And I mean, I think for a little while we thought that he might not make it out at 14 months from the hospital.

I mean, the seizures just kept coming and coming.

One lasted for 15 minutes and they at one point asked us to leave the emergency room because, you know, I guess we were probably in the way, but we, you know, we wanted to be by his side.

But they, they said, you know, y'all y'all need to leave.

And we literally didn't know if he was going to make it through.

We were sitting on the floor in the hallway just praying that that would not be the last time that we would be able to see him.

So we think that that I mean, you're never ready.

But we were definitely not ready of that town to lose him.

Like, we just felt like there was so much, you know, going on.

And he was doing pretty well.

Like still at 14 months, he was doing well.

But then those seizures hit and it was just kick started a whole different kind of direction.

So we started medication.

We started we when we got to children's, they life flighted him to children's and when we got there, he had a NG tube through his nose.

And so then they scheduled the G tube surgery like within a week or two afterwards once he got a little bit better.

So from that point on, like we, we had to stop feeding him orally to prevent aspiration and went to the feeding tube.

And also even after that seizure, he had it for 14 months.

We said, Well, we're going to do everything that we can until we can't go anymore.

So we went to baseball games at football games, went to basketball games.

We did all of those one year birthday party here at the bench, not the one near the two year two year.

Aubie came.

One year was the braves, Atlanta braves baseball.

We went to a Braves game because we got introduced to the Hudson Family Foundation.

So I think living in Auburn gave us also just more opportunities to do things as a family until about after right after two years, we slowed down pretty good just because we knew that we just didn't want to push it with him.

And so we had gotten just to do a lot of things that we treasure even to this day.

We have pictures just going to all these different events.

So and then we we gradually, from year three to four, struggled a lot more and had a little bit of a harder time but on then ultimately Porter passed away in November of 2016 at four years old.

So we watched Porter have to endure this condition for almost four years and died a little after his fourth birthday.

And just watching him and what he had to deal with and then the courage of his parents was a real inspiration for us.

I know a lot of people in the lab, including myself, when we thought about going home at night to watch the news or watch a game show, and then we thought, well, maybe we need to stay a couple more hours and get closer to the clinical trial.

There was no, no question about what we decided to do because we had Porter right here locally, living with us to show us how important the research is the potential was there for, what, 20 years?

And it wasn't until Doug Martin conceived of a way to treat the disease that something happened.

Here's one of these self motivating ingenious people who who see things that other people can't see.

One of the big steps forward in the research process was when I met Dr. Miguel Sena Esteves at a national conference at the time.

He was at Harvard Medical School, and he was working with mice that have GM1 He had developed a gene therapy treatment for the mice and I could tell by the results that he was presenting on his poster that this would be game changing if we could make it work in larger animals and in kids.

So we decided at that point to try his gene therapy approach in the cats that we have at the Scott Ritchey Research Center.

So Auburn has partnered with UMass Medical School from the very early days of this project, from almost step one, with vector modifications made by the people at UMass and then testing in the larger animal models here.

We also had a sheep model of Tay-Sachs disease now at UMass, where we did a lot of the early testing in the sheep model.

And so that was another order of magnitude of scale up in terms of the overall process.

So by the time we got into human patients, we had tested in mice, we had tested in cats, we had tested in sheep and even had tested in a few nonhuman primates to make sure that it was safe We had tried lots of different treatments before gene therapy, so we had tried purified enzyme replacement then we had tried little nanoparticles called liposomes, and we had tried bone marrow transplantation and stem cell transplantation.

Nothing ever made a dent in the disease progression of the animals at all.

And so we were a little bit skeptical when we tried gene therapy because nothing else had made a dent in the disease progression we knew within six months of treatment that the gene therapy was a different beast because the animals, after six months of treatment, often look normal, often looked as though they had no disease at all.

In fact, some of the animals looked so good that we thought we had misdiagnosed them and we went back and re-diagnosed them two or three times to make sure that they were actually affected animals.

They looked so normal.

Our animals are really happy and healthy.

This is not a painful disease, and the treatment is absolutely not painful whatsoever, and it improves their quality of life because they get to live as a normal cat and not have any of the stability or walking issues that the untreated animals have.

Untreated GMq animals typically reach their humane end point around eight months of age with our gene therapy, we've been able to significantly increase the lifespan.

And we have animals now living to 12, 12 and one half years of age, which is absolutely remarkable because that's normal cat lifespan versus the very much abbreviated untreated version.

Gene therapy can be lots of different things, but in our case, gene therapy is the use of a modified virus to deliver genes into cells.

And so it would be making a virus that normally is infectious so that it can only infect one time and then after that one time it can't reproduce itself.

So it's not damaging.

It just in this case is used as a delivery vehicle to get the genes into cells.

And we know what the gene defect is in many of these diseases, including GM1 and Tay-Sachs.

So we know what needs to be replaced in order to make normal protein or normal enzyme for those for those animals or those kids.

So we stick that normal gene into the modified virus, and then we inject the modified virus into the kids.

And depending on the route of treatment, it just looks like a fluid injection into a peripheral vein.

It's really not it's not invasive.

It's not a big deal.

The kids in the clinical trial at the National Institutes of Health receive an I.V.

injection for about 30 minutes and a lot of them sleep through the procedure and and never know that anything unusual has happened.

It's a one time treatment so that it doesn't have to be repeated over and over again.

Right now we're looking at cell culture to make our gene therapy product.

We actually use cells that are grown on these flasks, and we add three different plasmids together and add them to this media inside the cells.

The cells become a little virus factory and make that gene therapy product for us.

Then we'll harvest that cell pellet and run it through a purification column, and that gives us our final product.

With that product, we will then inject it into a cat like you see here with our IV treatment.

It's very easy, just a simple catheter into the arm and you're done one and done kind of treatment.

And after that we'll watch the cats throughout the disease progression and hopefully they never have any symptoms pop up, but we do evaluate that.

Downstream we want to look to see if we are able to restore that enzyme activity.

So that requires a lot of pipetting and different enzyme testings.

As you can see what's going on here.

We can do that process in the lab routinely, but that would be a research grade vector in the terms that we use a research grade vector.

To be able to treat kids or humans with them with that gene therapy, we have to go through a process called good manufacturing procedure GMP.

GMP takes things up to another entire level and is one of the reasons for the expense of the gene therapy right now, because all the regulations and rules and paperwork and procedures that you have to follow to meet GMP standards, that was one of the most expensive parts of getting things ready for the first clinical trial was preparing the GMP grade vector.

That can only be done at a few places around the country right now.

I expect as gene therapy becomes more popular, that there will be more facilities that can do it.

But at this point, that's both part of the bottleneck for slowing things down, and it's also part of the expense is having GMP grade gene therapy made.

At the National Institutes of Health they are experts on these types of diseases and an expert in particular named Dr. Cynthia Tiftt, who's probably the world's foremost expert on GM1 gangliosidosissince.

She has been a collaborator for a long time because she knew about the cat models and the mouse models and was very interested in gene therapy to eventually treat kids.

And so she is the principal investigator of the clinical trial.

So it's great to be at the National Institutes of Health because they cover all almost all of the costs.

If a patient can get to the NIH Clinical Center, then all of the costs of the clinical trial are covered at that point.

And truly, the world's foremost experts in GM1 gangliosidosis and other rare diseases of children.

You know, when I started my career in genetics, there were almost no genetic diseases for which there were treatment.

A few metabolic diseases had special diet therapies.

But in terms of actually reversing the course of the disease, not many.

And most of the genetic diseases we dealt with were pretty bad actors.

Over the course of my professional life, which is now almost 30 years, we have gone from having nothing to having kind of a tool box of therapies that can mitigate some of these things.

But the very hardest nut to crack have been the disorders that involve the central nervous system.

When I first finish my fellowship here at the NIH and went to work at Children's National across town, I was interested in lysosomal storage diseases from my work here.

One afternoon I'd been there two or three years.

One afternoon my neurology colleague literally carried a child into my clinic and put them on the exam table and said, Here this is one of your kids.

It was a child that turned out to have the infantile form of GM2 gangliosidosis, which is a very a cousin disease to GM1.

And that was kind of the inspiration when I had opportunity to leave Children's and come back to the NIH in 2009, we wrote a protocol to begin to look at the natural history of these diseases.

These are all lethal.

Normally when parents were given a diagnosis there was no therapy.

They were told, Take your child home, love them, you know, enjoy your child as long as you have them.

But no one actually looked at the way these children actually progressing their disease.

Well, if you don't know how the kids fall apart in their disease, how do you know when you've been successful if you institute a therapy, you don't.

So you have to be able to define what people call the natural history of the disease in order to target the things you're going to look at to see whether or not you're successful with the therapy we started to accrue patients with both gangliosidosis, and as it turned out, GM1 was more common than GM2.

So before long, we had 45 kids with GM1, and we started from there.

So the first clinical trial is underway now, and approximately 11 kids have been treated.

All of those kids have at least stayed the same after treatment.

Some of them have shown improvement and some have shown significant improvements, such as the ability to walk when they couldn't walk at treatment or the ability to swallow when they couldn't swallow well at treatment.

The first patient that was treated by the gene therapy was named Jojo And her mother is a physician in Los Angeles.

She has a little bit of a delayed form of the disease.

So it's not the most severe infantile form, but it's a little bit less severe, still very severe in most kids with this form of disease will die in their teens.

She was at a very severe disease stage when she was treated.

But after treatment, she we could see the improvements within a month of the treatment.

And it's been an amazing story to watch.

She lives in Los Angeles, so I don't get to see her on a regular basis.

But I do see periodically videos or pictures of the things that she's doing.

And so I can see the difference from one video to the next of how much she's improved.

She's doing things like walking with a walker and she could not walk at treatment.

She couldn't pick things up with her hands at treatment.

Now she's able to pick things up.

She can take a pill and swallow it.

Normally, she couldn't swallow normally before treatment.

Her swallowing was so bad at treatment that the doctors almost put a stomach tube in at that time so that she could get nutrition they decided not to.

They decided to give the the therapy a chance to work.

And that was a great decision because now she's eating and swallowing normally.

Just a fantastic success story for her so far.

Jojo was diagnosed when she was four year old, 2013.

But we first got introduced to Dr. Doug Martin and Miguel there was in 2015.

We found out Joleen was a GM1 patient rather late.

No one knew what it was.

And it took a lot of our own digging to actually find out that it was GM1.

We knew something was wrong, we did not know what it was.

A lot of disorders are scanned in or checked for in the infancy stage or right when a kid is born.

GM1 is so rare of a case that it's completely flown and under under the radar for all kids up to now.

And not only is it not diagnosed properly, there has been no treatment for it up to this point.

Good girl.

You work so hard.

I'm so proud of you, Jojo.

Once we find out there's an opportunity to have a expanded treatment for her, we were really excited.

Of course, as parents, we were concerned as well.

But given her condition was so bad at a time.

We're more, like, excited to have her be treated.

Her gene therapy was done.

In May 8, 2019.

Six months prior to that, her whole condition deteriorated quickly.

Every day she became a different girl.

She almost stopped eating and drinking.

She was on the floor all the time without knowing us and she stopped growing for actually not six months for two to three years prior to the gene therapy.

She'd choke on everything.

She started developing seizures, and she was just very fragile, dehydrated.

She had a big time heat and cold intolerance.

So we had to feed her every pretty much every hour.

And so though she's still losing weight and a cognitive function down the drain as well, and she can now recognize us and she had a seizure getting increased frequency of seizures.

Jojo had a one dose of an AV9 I.V.

injection and then she developed some like, you know, feeding issues and some from the immunosuppression, large dose of steroids.

She has some gastritis.

And, you know, so she was in a hospital in Orange County for another couple of weeks.

But then she started to turn around.

We did a very aggressive physical therapy and occupational therapy for her even up to now.

And so she started to maybe three months after that, she started to turn around.

She started gaining weight, build up muscle tone.

And her cognitive function was the first time actually we saw it got reversed so her attention span was much better and she became a lot more calm.

And the memory memories back and she's much happier girl.

So she she was able to eat on her own and drink on her own.

Probably the most important outcome measure is what can they do?

And we're looking at a at a scoring tool called the Vineland, which basically looks at adaptive behaviors.

You know, are you able to do motor skills or are you able to feed yourself?

Are you able to, you know, walk, run, able to speak?

And those are all age normed so we ask ourselves, we know these kids are going to be going down.

That's what we expect for their disease.

So what are we going to call success?

They don't go down as fast they just stop going down or they actually get better.

And all of those would be improvements, right?

If this is the trajectory down All of those would be improvements.

I would say most of the kids, not all, but most of the kids in the trial are going like this.

So we've arrested the disease as far as we can tell for how long, we don't know.

Jolene is actually the first child we treated and Jolene just passed her third year milestone post-treatment.

And she looks great.

I mean, we're very encouraged by how she functions, by her Vineland results, by her brain MRI's.

Pleasantly surprised, I would say.

Some of our other children are also stable A few of our children who had sort of the most severe disease, I would say are doing more like this as opposed to this knowing what we know about the natural progression of the disease.

So I think overall it's a success, but some kids have done better than others.

And I think, Jolene, I would put it in the category of better than others in fact, we were very surprised when we saw her back from her three year visit.

Jolene she's a very passionate girl.

Every day the moment she wakes up, she starts to smile.

And she enjoys every moment of her life just because the way she is, you know, she's she wants to live the fullness of her life.

She never had any temper tantrums.

She never been upset about everything, anything.

And I think she is going to school now and I think the biggest dream she has, she she loves fashion.

And she shared with us she wanted to be a like a fashion designer or somebody kind of, you know, like a kind of celebrity.

Dr. Tifft is the the principal investigator and Jolene, call her doctor grandma because she acts as a grandma to Jolene.

And there, you know, Jolene goes there every time since 2015 every time we go there and they would throw a tea party for Jolene.

And that just kind of makes her feel kind of like she's not in the a foreign place or some, you know, strange hospital setting.

She, Jolene has had to go through some things, you know, seven days in-patient, there was a lot of painful procedures, you know, including a lumbar puncture, general anesthesia, brain nerve conduction studies.

And those are kind of a traumatic and painful, though they try their very best to make it happen more like a, you know, a loving and fun environment and Jolene, every time she's looking forward to going back there, even though for us as you know, we we were frightened for each visit.

But Jolene, actually, she she loves her doctor grandma.

She loves the whole setting.

And at NIH they, she is Jolene will look forward to, you know, the play room the library, the bookstores there.

So the staff, they're friendly.

So they make it happen not only to treat her condition but also mentally kind of relax her, you know, give her the best environment to to make this happen.

It's very important not to give up hope because you know, I'm really glad to have my sister with me here today.

I don't I wouldn't be the same person I am without her.

And I'm I think I'm much way far better off with her influence than without so and she's my sister.

You know, you you can't give up on a family member that easily, no matter how how bad it is.

During Jolene's trial, we also managed to get off the clinical trial for 12 other GM1 kids around the world.

And I think just beginning with that, we've broken a huge barrier for a lot of other parents.

So if anyone else is watching and, you know, they have a kid with the same case, there there is treatment now.

So the real question is, is there a way to maximize the therapy by perhaps giving a second dose to try and target more neurons?

We know we're not hitting them all.

We're probably hitting close to them all.

And the ones that don't get the vector don't may have a way to receive the enzyme.

It's a phenomenon called cross correction, where cells sort of talk to each other and can pass the enzyme back and forth.

But that's probably fairly limited in neurons.

So the question is, are there are there different ways to deliver the vector or could we deliver it a second time that would target more more areas of the brain?

And that's a really open question because right now the immune system sort of precludes you being able to give the same vector, the same virus, the same treatment again, because the immune system like all of our immune systems.

Wait a minute.

I've seen this virus before and I don't like it and I've already made antibodies against it and it's out of there.

So in order to be able to do additional dosing and we're working on this we have to be able to figure out a way to trick the immune system into thinking that it's never seen this vector before and then not responding to it.

Well, it's every research scientist dream and prayer, but it never happens so I'm the lucky one.

Once I was in this field meeting the patients and the families and seeing the impact I can make completely changed my life and I can never do anything different.

This is a community that you never really want to be a part of because there's so much suffering involved in it.

But being a part of the community you get to meet the most fantastic people in the world.

So some of those are the parents and the patients and others are collaborators like my my coworkers at UMass Medical School.

They have been essential to every step of the process from the research grade, gene therapy development.

Ten years ago, to manufacturing the gene therapy for the clinical trial and making sure that all of the paperwork gets put into the document, documents needed for the Food and Drug Administration to approve the clinical trial.

They are truly among the top three or four places in the country for gene therapy.

And you know, it's it's it's incredible to see your life's work come to fruition.

I mean, I just have the most fantastic team and, you know, working with Doug Martin and Miguel Estévez and Heather Gray Edwards, and this is a ten year collaboration that we basically cobbled together with, you know, donations from Auburn, donations from UMass, donations for families to be able to put this trial together.

So it just means a lot to be able to see this come to fruition.

Dr. Martin has told us even when he's in these these at the hospital, when they're doing the injection, that he thinks about Porter And so I would say to a family that that's going through this.

I'm glad that there's hope and opportunity for them to try something instead of just walking away from a doctor's office.

Just absolutely devastated there's something that you can try.

And there is hope that your child would be able to live a normal life.

And I think that that's what everybody wants is for your child to be able to grow up and you be able to teach them and, you know, teach them all the life things.

And I think people have I know people have that opportunity now because of the work that they've done for sure.

In five years I would be overjoyed if this were FDA approved and every child with GM1 Gangliosidosis around the world would have access to it.

So instead of going into a genetic counselor's office and learning that your son or daughter has a fatal disease and probably won't live for more than three or four years, parents would then have an option to get this treatment and at least if it doesn't cure them entirely, at least it makes them a lot better so that they have a much better quality of life.

The GM1 gangliosidosis research is is an example of really being able to advance the base of knowledge on a specific disease.

And even though it's considered a rare disease, those people that are affected by it are dramatically affected.

Same is true for the cats that are affected.

So we see an opportunity when we can develop a gene therapy that targets an inherited genetic defect to be able to use the same strategies to target other diseases because we know there are many diseases that affect the neurons, the the basic cells of the brain that are responsible for nerve impulses.

And if we can develop a gene therapy that reverses a single gene defect for GM1 gangliosidosiss in a cat, we can translate that into the treatment of humans, which we've done and we've done it very effectively in collaboration with the University of Massachusetts and the National Institutes of Health.

But we can also find other diseases that affect the neurons and use a similar strategy, but maybe a different gene to to impart therapeutic success.

So this platform, while being specific or treating GM1 gangliosidosis, is also led us to developing new therapies for other genetic diseases and also infectious diseases.

We can use the same blueprint if you want to say for this gene therapy to be able to treat rabies, we're looking at making a rabies vaccination using this platform that would be more efficacious than the current standard.

We've been able to vaccinate mice and cats with that project and we've been we've seen over 100,000 times greater effect in the vaccination versus the standard conventional vaccine that they get at the veterinarian right now.

And so that's what makes the science so open and so exciting and such a great opportunity for our college to to continue to expand it.

One of the greatest success stories has been the involvement of undergraduate students in this overall process.

One of those undergraduate students that I'm thinking of right now her older brother died of GM1 gangliosidosis.

She was from North Carolina, and she knew about our lab and she wanted to come see if she could participate.

So the first step was for her to come and spend two weeks with us.

one summer.

She was so committed to finding a treatment for GM1 that she then came back to do her undergraduate degree at Auburn, worked with us for the entire time that she was an undergraduate in Auburn, and now she's in a MD PhD program at West Virginia.

So she is going on to continue the research that we started.

And she'll also be seeing patients with GM1, So those are those are part of the real success stories of of the overall research program.

And there certainly are places for other students who are interested in learning about research and gene therapy and neurologic diseases.

So any any student that has a curious mind and is interested in knowing why a student that asks the question why over and over again needs to think about veterinary medicine as a career, because it's so fascinating, it's so varied, it's so uniquely diverse.

There's a place for anybody in the veterinary profession, whether they be interested in dogs, cats, cattle, horses, pigs, sheep, goats, you name it.

It's an exciting profession.

It's one that links very closely with human health, and it's one that serves people through their animals.

And we're always looking for that inquisitive student, you know, a really good academic background to come in and ask us, hey, what do you do?

And let us tell you about it, because I think once a student learns what's going on in the College of Veterinary Medicine, their minds open up and they say, Hey, this is something that I want to do, and I would like to do it at Auburn because they're doing amazing work.

And so that's one of the things we're very proud of.

But I'd like to have people more interested in research especially, you know, you know, you want the kids to do well.

Well, the same thing.

I want young people to pick up the mantle and do what we're doing because it's important it's difficult, it's demanding, most time it's not rewarding, but it's important.