Since you're a subscriber to this Bloomberg podcast, we thought you'd be interested in a six episode sponsored podcast called Targeting the Toughest Diseases produced by Vertex Pharmaceuticals and Bloomberg Media Studios.

It explores the innovative tools, methods, and unique philosophy Vertex Pharmaceuticals is using to search for treatments for some of humanity's most challenging diseases.

Here's a recent episode.

Two year olds are a handful.

They're full of energy and full of laughter.

A lot of work for sure, but also a source of joy.

I definitely feel my calling in life was to be a mother, and I just feel so blessed to be able to have that opportunity to have a child.

So it's been great.

That's Rachel Benton, also known as Stetson's.

Small Stetson is his name, Stetson Corey Benton.

I've always liked unique names.

I never knew of anyone named Stetson before.

The thing about Stetson is, and he doesn't even know this yet, but he may have already saved his mom's life.

A routine medical test that Rachel only took because she was pregnant showed protein in her urine That led to further tests, a biopsy, and eventually a phone call delivering a diagnosis.

It was a.

Pretty quick conversation.

We know it is igiena fhropathy.

It's a rare kidney disease.

There is not a cure.

We don't have a cause.

The call was short, but for Rachel it changed everything.

Hi.

I'm Jordan Gospore, a member of the University of Southern California's Center for Health Journalism.

This is Targeting the Toughest Diseases a podcast produced by Bloomberg Media Studios and Vertex Pharmaceuticals.

In this series, we look at some of humanity's most challenging diseases and how Vertex, a Boston based biotech company, is using innovative tools, methods, and a unique philosophy to search for treatments and cures.

Today, we're looking at immunoglobulin A nephropathy, more commonly known as IgA nephropathy.

It's a progressive chronic kidney disease that, for too long, was underreported and under researched.

We'll talk to experts inside and outside of Vertex about the latest work being done in this field, But first back to Rachel's story.

At the age of thirty, Rachel bent and was living a great life.

She was a licensed mortgage broker running her own agency.

She owned her own house, and that fall she decided to throw a big Halloween.

Party and he came with one of our mutual friends and we sort of rekindled from there.

He was Tom, a guy she had dated on and off during her twenties.

And then it was the end of November of twenty twenty that he asked me to marry him.

A year later, they got married, and shortly after that, Rachel got pregnant.

During her pregnancy, Rachel had regular medical checkups, including routine yearine tests.

We did a yearine test, a twenty four hour year in test, and that's where you have to take this big jug home and you have to peece straight into this jug every time for twenty four hours.

And so I bring it to the doctor and they test it, and sure enough, they found protein in my earn.

The doctor told her she wasn't facing any immediate risk, so they agreed to put that result aside, focus on having a healthy baby, and that they would investigate further once the baby was born Stetson.

Corey Benton was born in May and as a new parent, Rachel's life instantly became a whirlwind.

Honestly, I completely even forgot about the kidney stuff.

But around the nine month mark she reached out to her doctor.

She retested her urine, which confirmed she still had protein in her urine, so they decided to do a kidney biopsy.

A biopsy is where a doctor uses a long needle to extract tiny pieces of tissue so they can do further tests.

Rachel got the results over the phone.

And he's like, you know, we did confirm some things.

You have a rare kidney disease called IgA nephropathy or I GAN.

So my fir question was, you know, what do I do now?

How do I stop this?

Is there a cure?

You know?

Just thinking of anything, like what's the next steps?

What about medication?

Blah blah blah.

And he's like, well, the answer to almost all of her questions was we're not sure or it depends.

I got off the phone and just cried.

I think for probably two days straight.

I just was overwhelmed with obviously the diagnosis and not knowing where this would take me in life.

What the next You know, twenty four hours would look like a year or ten years.

You know, how is this going to affect me in my day to day life and my son and my husband.

She's adjusted her diet and takes medication to address her blood pressure and cholesterol, but the progress of the disease is variable.

At one point, Rachel's kidney function dropped thirty points over two months.

The doctor told her that at that rate, she'd be needing dialysis within a year.

She's rebounded, but she doesn't know if that recovery will hold.

She also deals with fatigue, not just new mom tiredness, but debilitating fatigue, where she'll sleep for twelve hours and still need a midday nap.

In fact, Rachel says that for a couple of years before her diagnosis, she was already dealing with extreme tiredness, but never really considered it a medical condition or something that needed attention.

In hindsight, she wishes she had gotten it checked out.

Looking forward, her long term health and her ability to be the kind of mom she wants to be is uncertain.

I have my days where I just feel very, very guilty being a other to him with a rare disease and not knowing in a year, ten years, however long, how I'm going to be and how active I get to be in his life.

Every day.

I just try to make the best of it though, and you know, whatever he wants to do, I put on a smile and try to push.

Through immunoglobulin A nephropathy or IGAN.

It's not a high profile disease.

It's a pronic kidney disease that historically has not been well understood, but that's changing.

So I do clinics, so I see patients with gramariala disease.

I run clinical trials, and I have my research work at the university and the laboratory.

That's doctor Jonathan Barrett.

He's based at the University of Leicester in England and as a world renowned leader in kidney research.

So most of my career, no one was really interested in Nigeria property apart from a few people.

Now it is you can't move at a kidney meeting without people talking about igenafropathy.

One reason it was so under researched is that in the early stages, symptoms are often hard to detect.

Normally, the patients I see have no idea why they're coming to see a kidney doctor.

In many cases, it starts with an asymptomatic person having a urine test, like in Rachel's case, with a routine urine test during pregnancy.

Perhaps you've joined a new gym, you get a physical, so you want to get a mortgage.

You might have a job that requires you to have a physical and someone dips your urine and they don't wait a minute, there's blood and protein in here.

Here's what we do know about the disease.

So each kidney contains about a million filters and they are continually filtering the blood to generate the urine, and in igenafropathy, this protein called IgA starts sludging up those filters and stopping them from working properly.

And if the filters don't work very well, they become leaky and blood and protein can appear in the urine.

Over time, sometimes months, sometimes years, your kidney function declines.

Some patients do really well with igenafropathy, and others end up on dialysis relatively quickly.

And that's the bit we haven't quite worked out yet.

In fact, we know the majority of adult patients with igaafhropathy will progress to instage kidney disease, which requires them to go on dialysis or get a transplant within twenty years of diagnosis.

Doctor Barrett says there is evidence of a genetic component, but the connections aren't strong enough to do genetic screening right now.

The only way to diagnose iganaphropathy is with the kidney biopsy.

But what we think is that the major driver for this disease is the type of ida we normally produce in our gut and in our respiratory tract that normally gets into our sputum, into our tears, into our saliva.

It's there to stop bugs entering the body, and it does a very very good job.

But in igenic property, some of that ida actually gets into the bloodstream.

When it's in the bloodstream, it's a bit out of place, and it tends to stick to itself, to stick to other proteins.

There are antibodies in the circulation it sticks to, and that forms these large what we call immune complexes, which are essentially big aggregates of protein.

If you've got big globs of protein, it's completely reasonable to think that those globs approtein are going to start clogging up the filter, which is exactly what happens, and when they clog up the filter, there's inflammation, they're scarring, and that's what eventually causes kidney failure.

For people diagnosed with IgA nefhropathy.

The biological effects are only part of the problem.

The big challenge is actually the impact on mental wellness.

Because if you're a young person and I tell you you've got this disease, it's incurable.

There's a risk it could cause kidney failure in the future, but I can't tell you when you might need to go on diallasis have you get your transplant, but I can't tell you when.

That sense of uncertainty can be absolutely devastating for young people.

You imagine developing your career, wanting to pay that big amount of money for a house, getting married, thinking about children, and you have this threat hanging over you of a disease that the doctors can't really predict.

Addressing that fear and uncertainty requires showing patients there is a way forward, and that's what the team at Vertex is doing.

Igienephropathy represents exactly the kind of medical problem Vertex is targeting.

There's a long history of research to build on there's new technology available or Vertex thinks they can develop it.

There's a large unmet need, and Vertex thinks it may be possible to tackle the underlying disease.

Simply put, Verticy's goal is to help people suffering from serious diseases, and we do that by investing in the scientific innovation to create what we believe could be truly transformative medicines for people with these diseases.

That's Mark Bunnage.

He's the head of research at Vertex Pharmaceuticals and leads research on the company's pipeline of serious diseases.

Now, we focus on cause of human biology and on human validated targets, and then we ask the question what's the right approach to take, and we are completely metalitiagnostic.

We'll use whatever is the right tool in the toolbox if you like, to address their biology and then to come up with a transformative therapy.

Earlier, doctor Barrett explained how igianophropathy occurs.

It's a build up of what he calls big globs of protein that deposit and cause injury to the filters in your kidneys.

But how can we stop that from happening.

To answer that, I sat down with doctor Maniche Maski.

He's a board certified nephrologist helping lead Vertex research into IgA nephropathy.

Doctor Maski explained that B cells, an important part of our immune system to fight off infections, can lose control and produce antibodies that hurt our own organs, in this case, the kidneys.

Can you tell us a little bit about where the field is going and what's being done for people living with IgA nephropathy.

Absolutely, we now understand that loss of B cell control is what leads to the downstream mechanisms resulting in kidney injury and kidney function loss.

So lots of research has been performed to try to understand what is influencing the B cell to lose control.

It turns out that two proteins called Bath and april are key drivers.

Okay, so B cells are a type of white blood cell that helps power our immune system.

Can you tell us a little bit more about what Bath and April are and how they're involved in B cell control and how all that relates to iganephropathy.

So, first, Jordan, you're absolutely right that B cells, when they're doing what they're supposed to do, protect us from infections.

They make cand of bodies that help us neutralize various pathogens.

When B cells lose control, they can set off a cascade of events that result in processes that harm the body, so called autoimmune diseases.

Bath and April are two similar but distinct proteins that control the life cycle of the B cell.

So bath more in the early stage of development and maturation of the B cell and april more in the later stage of the B cell development all the way through to becoming an antibody secreting cell.

Bath in april really seem to be two of the most critical proteins driving this transition from something that would protect us to something that would actually make antibodies that will harm our native tissues.

This is a complex scenario.

What's the innovative thinking that Vertex is considering here.

We know that the levels of bath in april are actually elevated in people with ig and ephropathy, and that these levels correlate with measures of kidney function and damage.

So through that we believe both of these drivers are involved in uncontrolled B cells.

Not Bath alone and not april alone.

There's a need to cast the widest net to catch the main actors involved in the pathogenesis of IgA and nephropathy.

What we hope to see with this approach is the potential to restore immune balance for our patients and give them the best chance at remission in the protin area, which is the protein spilling in the urine he maturia, which is the spilling of blood in the urine with associated stabilization of kidney function.

For Rachel Benton, living with uncertainty has become a constant burden.

It really scares me.

For my son, I feel like I let him down.

I guess, you know, it's not fair for him to have a mom that is going to be sick for the rest of our life.

It might not be bad today, but we don't know about tomorrow, you know.

And I just I feel guilt in that aspect of him just not having a healthy mom.

Same for my husband, for him to have a wife that just doesn't healthy and it breaks my heart for them really.

But I try to stay positive and take care of myself as much as I can, but it definitely does play a huge role on your mental health for sure.

Day to day.

Some days I can be like, you know what, I am a warrior I got this.

Everything's great.

In other days it's like I am not okay, and I feel like I could just crawl under a rock and stay there.

Rachel, like a lot of people living with IgA nephropathy, has become an advocate, encouraging others to get checked.

All of my friends because of this, I'm like, please get your yearlys done, but also ask for that urine test.

You know, if you see any sign of protein in your urine, just double check it.

Why not?

Exactly why not?

Kidney health is not top of mind for most people, but it's worth talking to your doctor about.

You can also go to Vertex's website vrtx dot com for more information on Vertex's commitment to IgA nephropathy and other serious kidney diseases.

This is Targeting the Toughest Diseases a podcast from Bloomberg Media Studios and Vertex Pharmaceuticals.

If you like what you hear, subscribe and leave us a review.

I'm Jordan Gospore.

Thanks for listening.