FDA Approves CRISPR-Based Medicine For Treatment of Sickle Cell Disease (statnews.com) 43
An anonymous reader quotes a report from STAT: The Food and Drug Administration on Friday approved the world's first medicine based on CRISPR gene-editing technology, a groundbreaking treatment for sickle cell disease that delivers a potential cure for people born with the chronic and life-shortening blood disorder. The new medicine, called Casgevy, is made by Vertex Pharmaceuticals and CRISPR Therapeutics. Its authorization is a scientific triumph for the technology that can efficiently and precisely repair DNA mutations -- ushering in a new era of genetic medicines for inherited diseases.
In a clinical trial, Casgevy was shown to eliminate recurrent episodes of debilitating pain caused by sickle cell, which afflicts approximately 100,000 people in the U.S., a vast majority of whom are Black. The therapy, whose scientific name is exa-cel, is described as a potential cure because the genetic fix enabled by CRISPR is designed to last a lifetime, although confirmation will require years of follow-up. The FDA decision comes three weeks after regulators in the U.K. were the first to clear the drug. Approval in the European Union is expected next year. The FDA is also expected to rule on exa-cel as a treatment for beta thalassemia, another inherited blood disorder, by March 30.
The FDA on Friday also approved another sickle cell treatment, a gene therapy from Bluebird Bio called Lyfgenia. Patients will now have the option of two cutting-edge therapies that provide potentially curative benefits. Scientists Emmanuelle Charpentier and Jennifer Doudna published their first CRISPR paper just over a decade ago. In 2020, the research won the pair a Nobel Prize. Reflecting on the approval of Casgevy, Charpentier told STAT via email that she was "excited and pleased" for what it means for patients and their families.
In a clinical trial, Casgevy was shown to eliminate recurrent episodes of debilitating pain caused by sickle cell, which afflicts approximately 100,000 people in the U.S., a vast majority of whom are Black. The therapy, whose scientific name is exa-cel, is described as a potential cure because the genetic fix enabled by CRISPR is designed to last a lifetime, although confirmation will require years of follow-up. The FDA decision comes three weeks after regulators in the U.K. were the first to clear the drug. Approval in the European Union is expected next year. The FDA is also expected to rule on exa-cel as a treatment for beta thalassemia, another inherited blood disorder, by March 30.
The FDA on Friday also approved another sickle cell treatment, a gene therapy from Bluebird Bio called Lyfgenia. Patients will now have the option of two cutting-edge therapies that provide potentially curative benefits. Scientists Emmanuelle Charpentier and Jennifer Doudna published their first CRISPR paper just over a decade ago. In 2020, the research won the pair a Nobel Prize. Reflecting on the approval of Casgevy, Charpentier told STAT via email that she was "excited and pleased" for what it means for patients and their families.
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Symptoms:
Anemia. Sickle cells break apart easily and die. Red blood cells usually live for about 120 days before they need to be replaced. But sickle cells typically die in 10 to 20 days, leaving a shortage of red blood cells (anemia). Without enough red blood cells, the body can't get enough oxygen and this causes fatigue.
Episodes of pain. Periodic episodes of extreme pain, called pain crises, are a major symptom of sickle cell anemia. Pain develops when sickle-shaped red blood cells block blood flow throu
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An interesting issue is that one copy of the sickle-cell causing gene confers malaria resistance. It's two that cause issues.
What would be really nifty would be finding a way to leave the resistance (and making it a dominant trait) while removing the risk of sickle-cell.
I suspect we're quite a way off from that kind of DNA tampering, though. Right now we seem to be in the "we don't really understand English, but we know how to copy a paragraph from someone else's essay" phase of DNA alteration.
Re: Moderna == Operating System (Score:2)
Pretty much a coincidence, sickle cells are shaped so strangly that Malaria cannot infect, and this is the adult red blood cells.
And this is where the treatment is cool, one gene causes the body to go from the child blood cells to the adult blood cells, which have the problems.
Switch off that one gene and you go back to making the original child based blood cells, ( I think it's the beta cells, the adult are gamma, been a bit since I read the original article)
You can live a pretty normal life on the beta c
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The funny thing is that humans didn't even invent this - we just reapplied it. CRISPR-Cas9 comes from bacteria that evolved a clever defense against viruses (retroviral bacteriophages). Basically, large chunks of the bacterial DNA are these palindromic repeated sections (CRISPR is literally "Clustered Regularly Interspaced Short Palindromic Repeats"), so when a retrovirus tries to insert into their DNA, it probably lands there. But that's a trap: these repeats don't get expressed to create proteins, but rat
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It is a terrible disease. Yes.
Therefore we should allow big pharma and bill gates to profit from distributing an insufficiently tested drug. Does not follow.
Release untested drug or no drug at all is a false dichotomy.
Follow the established protocols. Make sure it isn't more harmful than doing nothing. Make sure it actually fixes something. We are people not guinea pigs.
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Therefore we should allow big pharma and bill gates to profit
I don't see the government spending the tens of millions of dollars doing the research so someone has to. If you're against profit you can start up your own company and give your drugs away for free.
from distributing an insufficiently tested drug.
Which of course isn't happening. Every single drug in the U.S. has been sufficiently tested. Unles your definition of sufficiently is thirty or more years of seeing what happens.
Follow the established pr
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I'm responding to this, "In this case a risky treatment still gives you better odds than doing nothing" from above.
Would you like to try again?
Life is not being a guinea pig. That's just stupid. Life is full of unknowns but putting money in someone's pocket to be their guinea pig is an unnecessary unknown. Please stay on context and don't straw man.
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It's called "science". Try it sometime. But you're a thalidomide baby so it makes sense.
Re:Moderna == Operating System (Score:4, Insightful)
how is this cavalier? First, this is for a nasty debilitating disease. Given how terrible severe sickle cell anemia is, the chance of the cure being worse than the disease is virtually non-existent. You have a better chance of getting in an accident crossing the road that by this technology (yet nobody avoid roads, do they?). This is the first approved technology, and CRISPR gene-eidting has been a thing for over a decade prior to this.
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You're trying to use logic with an anonymous, anti-vax troll.
Don't waste your time.
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how is this cavalier? First, this is for a nasty debilitating disease. Given how terrible severe sickle cell anemia is, the chance of the cure being worse than the disease is virtually non-existent.
So is the affordability. Solutions are deemed quite cavalier, because greed.
Doubly so for cures, since perpetual treatments are greatly preferred, because greed.
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Doubly so for cures, since perpetual treatments are greatly preferred, because greed.
I hate this BS line. You do realize (I guess you don't...) that those of us working in medicine dedicate much of our lives to curing patients as best as possible. If I have two options, one which cures and one which palliates indefinitely, I typically choose the former. We aren't sitting here thinking "hmmm...how to milk this person for a boat payment..."
We have literally run trials on drugs that were considered lifelong therapy to see if we could safely stop them (Disclaimer: I am not saying every drug allows this, but we DO consider it where feasible):
https://www.ncbi.nlm.nih.gov/p... [nih.gov].
"An attempt to discontinue therapy can be considered after the achievement and long-term maintenance of DMR (deep molecular response). The concept was established with the Stop Imatinib 1 (STIM1) trial. After a median follow-up of 77 months after stopping TKI therapy, 38% of patients maintained a molecular remission. In this trial, patients were eligible for treatment discontinuation with negative results of a sensitive quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) sustained for 2 years before stopping. After this innovative pilot study, multiple trials were conducted, each with different entry criteria and definitions of relapse, prompting a restart of TKIs. Concurrently, PCR methodology and definitions of PCR sensitivity were standardized in order to harmonize recommendations for treatment discontinuation and increase the safety of stopping procedures."
Baby steps (Score:3)
Wait until we have enough confidence to edit the germline so your kids can't get it.
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Wait until we have enough confidence to edit the germline so your kids can't get it.
Sickle cell disease is not normally directly inherited.
It is a recessive gene. The disease only manifests if both copies carry the trait.
About 8% of African Americans have a single copy, and 0.2% have two copies.
So if an African American with the disease mates with another African American, there is a 4% chance a child will have the disease.
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Umm... That's 1/20 black kids with sickle cell. I suspect you made an error multiplying 0.08 * 0.08, which should have come out to 0.0064 or 0.64% and not 4%
Which would still seem to indicate a LOT of people are getting tested or checking family history prior to having kids (and good on them for being so responsible!), because that's 1/3 the rate you'd expect based on random pairings.
Unless I've ALSO made a math error somewhere, which I am prone to do.
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Umm... That's 1/20 black kids with sickle cell.
No. It is 1/20 of kids of ONE PARENT WHO HAS THE DISEASE, not of the general black population.
multiplying 0.08 * 0.08, which should have come out to 0.0064 or 0.64%
Nope. The rate for the general AA population is 0.08*0.08/4 = 0.0016 or 0.16%.
You need to divide by four because only a quarter of such pairings result in two copies of the bad gene.
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I wasn't aware black people only mate with black people.
Re:Baby steps (Score:4, Informative)
I wasn't aware black people only mate with black people.
They mostly do.
95% of black women mate with black men.
90% of black men mate with black women.
That is a higher rate of endogamy than other minorities such as Asian-Americans and Hispanics.
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How many black women mate with black women?
How many black men mate with black men?
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How many black women mate with black women?
How many black men mate with black men?
We are talking about passing genes, which means children.
Men mating with men rarely results in offspring.
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Um...that is the very definition of "directly inherited". It literally is inherited from the parents, either by receiving the single recessive gene that both parents carry (e.g. Ss + Ss = ss) or from a carrier parent + expressed parent (e.g. Ss + ss = ss) or even two expressers (e.g. ss + ss = ss). Yes, I have seen parents who both had the disease have children and yes they did so knowing their child would 100% inherit the disease.
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If you'd read anything about the therapy, you'd realize it involves removing stem cells from the patients' bone marrow, editing the genes in them, then transplanting them back into the patient.
At no point do they remove a patient's testicles/ovaries and edit the genes there.
It is literally impossible for this treatment to be passed on to a child.
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If you'd ready anything about my post, you'd realize it involves talking about the future.
At no point does it suggested the current treatment is heritable.
It is literally impossible to interpret the post otherwise.
Where's my Secure DNA Bootloader? (Score:2)
It is a brave new world. How long until we will need to patch our DNA with a Signed and Secure DNA Bootloader?
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There's no point. The human dna boot sequence occurs only once per unit, often in an unscheduled and haphazard manner such as in a back seat or club bathroom after heavy alcohol or other substance consumption.
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There's no point. The human dna boot sequence occurs only once per unit, often in an unscheduled and haphazard manner such as in a back seat or club bathroom after heavy alcohol or other substance consumption.
And usually with unknown random accompanying birth defects added at not charge.
Francis Mojica (Score:3)
https://en.wikipedia.org/wiki/Francisco_Mojica
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He didn't discover its DNA editing properties nor was he first to spot the existence of CRISPR sequences.
So... Again? (Score:2)
Go ahead and mark this troll, but I gotta say it...
We gonna try it on black people first?
I hope it's just a low-hanging fruit, good test case for CRISPR and not that.
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You aren't wrong but I literally just had to sit through a training on this subject. Yes, it is potentially highly problematic to pick your trial subjects from a pool which is, statistically, economically and socially disadvantaged compared to the researchers. However, it is still considered potentially ethical if there is a high benefit and if the research requires involvement of the vulnerable group. Yes, appropriate safeguards and considerations must be made.
But you're in a Catch-22 if you can't perform