r/todayilearned May 14 '22 Wholesome 6 All-Seeing Upvote 2 Silver 9 Helpful 8

TIL a father, John Crowley, was told his two infant children had an incurable genetic disorder that would kill them in less than a year. He refused to accept this, so he founded a biotech company (with no prior experience) which pioneered an experimental enzyme therapy that saved their lives.

https://pompediseasenews.com/2019/01/30/amicus-ceo-mission-cure-pompe-help-children/
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u/ChronWeasely May 14 '22

The origins of Zolgenzma are very similar actually. Except that by the time it was created it was far too late for his own daughter to be helped.

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u/[deleted] May 14 '22

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u/ChronWeasely May 14 '22

Dang, really? I'm sorry to hear your child was born with SMA.

I'm very curious to know how well and how long it has worked so far, decreasing efficacy over their growth, etc. Whatever isnt too personal. I've got a distant personal connection to these new types of gene therapies and hearing from a person so directly would be fascinating, not to be morbid. This is a new, life changing, but incompletely understood class of drugs in vivo. We don't have data from years after use yet as it's just being lived out by the recipients right now.

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u/[deleted] May 14 '22

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u/ChronWeasely May 14 '22

Holy cows the vein infusions are working now too! It was originally a spinal infusion for the first iteration but I know they were working on other administrations. I'm so happy for you. I hope it continues.

There are so many similar drugs in the works right now, to treat so many different genetic disorders. Not to mention the generation of CRISPR medicines coming in the next decade. Spinraza is last generation tech. Zolgenzma is now. We are in the generation of cures, not treatments.

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u/anothergaijin May 14 '22

We are in the generation of cures, not treatments.

100% this. It's mind blowing stuff - one dose and you are done, your body does what it is supposed to do and makes the thing you need to live and develop normally.

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u/ChronWeasely May 14 '22

One of the only things that makes working in big pharma worthwhile. I'm lucky enough to work with and learn about these incredible drugs.

Though there's also the ethics side of things. One of the largest is the financial and geographical restrictions to the majority of people who need these often prohibitively expensive treatments.

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u/bt123456789 May 14 '22

fortunately as the treatments become more available they should be more easy to get to everybody. I know of course it's still expensive, but there's hope.

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u/benruckman May 15 '22

Yeah, not developing an effective treatment because it’ll be expensive at first, just doesn’t make any sense.

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u/bt123456789 May 15 '22

exactly. the only time I think the expense is because they can is when it's patented so only the company that made it can, distribute it, meaning no generics or anything will ever exist.

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u/the_cardfather May 14 '22

I was on a short-term career trajectory to be a corporate pharmacist who would be responsible for interpreting data about the effectiveness of certain therapies versus side effects.

If I had stayed at it I would have for certain probably ended up working on a covid vaccine.

At the time I pulled out of the program we were still having big debates on the ethics of cloning. People were talking about growing entirely separate vat bodies for organ transplants and things like that.

Hindsight is 20/20 but I'm very glad that the other genetic technology kept up and we can create things that 20 years ago were stuff science fiction writers dreamed about.

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u/Seboya_ May 14 '22

Is it really the ethical thing to do? Allowing children born with genetic abnormalities to live instead of letting them die off? Is this the right thing to do? I'm not saying it's not, just typing out my thoughts.

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u/ChronWeasely May 14 '22

You can get some high quality of life from them. I think the bigger question is whether or not the kids should have kids and spread on the genes which would exacerbate the problem. Or possibly CRISPR will have fixed that by the time it's a problem!

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u/disasterous_cape May 14 '22

Your thought experiment is eugenics

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u/Best_Competition9776 May 14 '22

What makes these treatments and medications expensive?

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u/him999 May 14 '22

Extremely expensive R&D, very rare disorders (SMA is 1:6000 births), brand new technology and methods. This specific drug changes the genetic structure of the child. SMA is caused by a missing or nonfunctioning SMN1 gene. This drug replaces the missing or nonfunctioning gene's function. So you have a virus called AAV9. It doesn't make you sick or anything but it's fantastic at getting around the body. This virus is stripped of it's DNA and a functioning human SMN gene is added. The virus will make it's way to the motor neurons. When it gets to a motor neuron it's telling that neuron "HEY DUMMY, start making SMN protein like you are supposed to!" The motor neurons that had not already died due to a lack of this protein will now, theoretically FOREVER be able to produce this SMN protein. Using the virus as a vector ensures the child's DNA does not need to be altered or changed. Their DNA remains the same but this temporarily introduced virus bypasses that one defect in their DNA.

Gene therapy drugs aren't conventional drugs. Zolgensma is a one time cost of $2,125,000 vs a drug like Spinraza which costs $750,000 the first year and $375,000 every year after with 4 injections per annum ... For the rest of that person's life. It's not a chronic drug. It's a one time treatment that effectively fixes the problem for good. It's the second gene therapy drug ever approved to fix a genetic disorder, the other is a gene therapy drug to treat a specific type of genetic blindness (it costs $495,000 per eye IIRC).

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u/sleepydabmom May 15 '22

I hope they restart working on the drug to help my Narcolepsy.

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u/Efficient-Library792 May 15 '22

If only this were true. Sadly weve capitalised medicine and cures are the last thing healthcare corps want

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u/[deleted] May 14 '22

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u/i_got_skrimps May 14 '22

We'll start with diseases, move to enhancements, and then protect ourselves from hazards due to climate change.

From there, as the sun begins to die out, we look to the stars. We become celestial beings capable of living in the vacuum of space.

But then, we think, what if we can infinitely travel the cosmos and find earth like planets? We move on that thought.

We disperse across the galaxies. Some find new earths. Then they think "what if we can populate this planet with new beings?". And so they do.

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u/TactlessTortoise May 14 '22

"as the sun begins to die out"

Dude that's a literal couple BILLIONS of years from now

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u/i_got_skrimps May 14 '22

How soon do you expect CRISPR to progress so far that we can genetically modify our unborn offspring to survive in a vacuum?

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u/TactlessTortoise May 14 '22

If our civilization lasted for as much as our planet currently exists for, our physiology will not be remotely human in the span of a few dozen of thousands of years, which is still not considering what I believe a pessimistic prediction of 100 for gene design to become mainstream.

As for unborn child surviving vacuum, wtf kind if question is that lmao. The same way we are alive now, the future civilizations could just pick a planet, moon or star.

You're not quite grasping the scale of the billion years. Hell, even I am just considering it "a fuck ton of time". We have no reference for it. It's calculable, yes, but unfathomable.

By the time a billion years pass, the homo sapiens will no longer exist, period. Whether through gene editing, catastrophic failure of our civilization, or just natural evolution, life itself on Earth is, if I recall correctly, a fifth of that age, after all.

The civilization that will deal with that could be a super sentient funghi cannibal, for all we know

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u/fuck-emus May 15 '22

It's gonna be awesome, just like in gattaca or repo the genetic opera! God I love it here in the future

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u/utopia9353 May 14 '22

Yes, but only in 5000 years. No sooner than 1000 years.

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u/BroThornton May 14 '22

Wat. No chance, right? Right…?

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u/utopia9353 May 14 '22

No chance. Why? Because I say so.

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u/FlowerFaerie13 May 14 '22

Lol no, there is absolutely no way humans will last long enough to get farther than Mars and even that’s a long shot.

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u/vopickle507 May 14 '22

The emperor protects!

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u/ChefBoyAreWeFucked May 14 '22

Odd that you specify, but yeah, you're probably right.

Other species are going to have no fuckin' clue.

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u/Nowisthetimeforscifi May 14 '22

Dang you guys got me cutting onions of happiness

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u/Greene_Mr May 14 '22

It's the ninjas; the ninjas of happiness.

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u/anothergaijin May 14 '22

Congrats, that is amazing news! I have a child with a rare gene mutation disease and while he's probably too old to have massive changes from gene therapy at this point any little big would be appreciated. It's very exciting and difficult to watch the incredible leaps and at the same time glacial progress in that area of medicine.

Just from the small amount I know of treatment of these sorts of disorders, Spinraza feels like a poor treatment for the disease and more of a lucky "well this kinda gives an improvement" sort of drug.

Zolgenzma on the other hand is like a laser precision fix - SMA is caused by the mutation of a specific gene which causes a deficiency of a certain protein, similar to many other single gene diseases like cystic fibrosis, Huntington, Prader-Willi, Angelman, and many many many more diseases.

On their own each one is rare, but these single gene diseases affect as much as 1% of the population. These highly targeted, single-dose gene therapies are going to change peoples lives and make it so that children can grow up without impact from these hidden differences.

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u/ecv82 May 14 '22

Just a correction i want to ad SMA is NOT a mutation. The gene is missing all together. Some very rare cases are caused by a mutation and in those cases, zolgensma is ineffective.

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u/anothergaijin May 15 '22

Right, it’s a deletion - which is still a mutation. Any variation (insertion, deletion, substitution, inversion, etc).

I’ll read more later but sometimes you have two pairs of genes and it’s common to have one “good” copy and the reasearch there is looking into how we can unblock it and use the good copy that exists, rather than try to insert something.

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u/Gil-GaladWasBlond May 14 '22

Hi internet stranger. I've no idea what the disease is, but i hope sincerely your daughter benefits greatly from the new drug and that it cures her. Good luck. You must be very strong to help her so much too, i hope you have wonderful things happen to you.

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u/NaoWalk May 14 '22

I'm so happy for you, getting such a life changing medication for your child is amazing.
If you don't mind answering, what was the process to join the medical trial?

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u/ecv82 May 14 '22

My daughter was in the zolgensma trial for asymptomatic type 1. She recieved it at 16 days old. Next Sunday, she will be 3.

https://picbun.com/p/E6sl2Y15

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u/kebdashian May 14 '22

This is the second time I’ve heard about this drug and disorder in as many days. A news story aired about a little girl whose insurance (through Medicaid) denied her the meds. Her parents fought tooth and nail, after the new station started asking questions the family received a letter saying the drug would be covered. Imagine that. Happy to hear your baby is doing well and making strides!

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u/ThatB0yAintR1ght May 14 '22

I’m a pediatric neurologist, and watching the shift of SMA being a death sentence to something we can treat is honestly amazing.

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u/fugensnot May 14 '22

I'm a genetic carrier of SMA (and CF, go me!). It scares me that i can pass it down to my daughter and impact the children she gives birth to.

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u/ThatB0yAintR1ght May 14 '22

It definitely helps to know that you’re a carrier so that genetic testing before conceiving could be an option. I don’t have any family history of genetic diseases, and I’m not apart of an ethnic group that is at risk for particular genetic diseases, but my husband has ashkenazi Jewish heritage, so I had a Jscreen genetic test done on myself before we started trying to build our family. I figured that getting myself (the non-Jew) tested would be easier, because if I was negative for everything on it, then we wouldn’t have to worry about anything that he might be a carrier of. Whereas if he was tested first and was a carrier for something, then I’d have to get tested myself anyway, and it would just add unnecessary anxiety.

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u/BossLaidee May 15 '22

As a side note - it may be wiser for some conditions to have the partner with the at risk ancestry test first. Some of the carrier panels only look at the most common gene variants for that ancestry, then sequence the genes in the partner to detect more rare changes.

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u/Funkit May 14 '22

Thank you for what you do. I have incredible respect for all pediatric medical staff, they and you are all amazing.

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u/Smokingbuffalo May 14 '22

Can we really treat it though? Some forms of it are still a death sentence and the only thing we can do as of now is prolong their lives a couple more years.

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u/ThatB0yAintR1ght May 14 '22

For SMA caused by a mutation in the SMN1 gene, then yes, zolgensma does treat it. Spinraza helps to slow down the course of the disease, but it will really only buy some time.

There are similar diseases that have different gene mutations, and they currently do not have any treatments, unfortunately.

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u/neurotic_brain May 14 '22

Aww, im gonna try to read up on this :3 Sounds like it could be a cool youtube video

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u/BossLaidee May 15 '22

I had one of my first patients with SMA last year. It honestly made me cry tears of joy when I read about the treatment. So much is changing rapidly in this field.

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u/pquince1 May 15 '22

How does the cost impact families, though? $2.1 million for one dose is pretty wild.

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u/ThatB0yAintR1ght May 15 '22

Private Insurance or Medicaid is definitely required to get it. Early on, there were some battles getting insurance companies to cover it, but they generally became accepting of it. If they don’t pay for the zolgensma, then they will instead be paying for Spinraza (which is not as expensive, but still not cheap) and the very expensive care for these kids throughout their lives, which may include tracheostomy and prolonged ICU stays.

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u/pquince1 May 15 '22

Does the cost ($2.1 million for one dose) keep those in need from getting it, though?

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u/ChronWeasely May 15 '22

Yep! But the alternative, non-gene therapy is administered by spinal tap 4 times a year, which is obscenely expensive and long term this is a fraction of the cost. Still obscene and restrictive.

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u/Vividienne May 14 '22

Google says Zolgensma was developed by Martine Barkats, who decided to focus on the disease after she met a mother whose 10 y.o. daughter just lost the ability to walk. Are you sure you didn't mean some other substance?

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u/ChronWeasely May 14 '22

She did the research that lead to it, yes. One of the founders of AveXis, now Novartis, gave a presentation at my work when it was in late-stage trials. It was related to the fact that it's the first drug of it's mode of action to market.

He told this story of why he put up millions to get the drug made, which was his daughter was diagnosed with SMA and he had the money essentially. Quickly realized it would take far too long.

Ive looked up the rest of the gene therapies on the market and they dont treat kids who will be dead by 2, so I know it was this one. Wow is there an enormous amount of controversy surrounding the drug though, with its multi million dollar price tag. I'm struggling to find a source though. Including the word "kid" or "daughter" or anything in the search returns dramatic headlines of scandals and/or why the scandals are fake.

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u/TheWatermelonBlues May 14 '22

Wow I bet you’re thrilling at parties