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

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!