[Topic name broadened] Novel, potentially game-changing, advances in biomedicine

[BacktoCricaddict]

https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

 

Quote

Today, the U.S. Food and Drug Administration approved two milestone treatments, Casgevy and Lyfgenia, representing the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older. Additionally, one of these therapies, Casgevy, is the first FDA-approved treatment to utilize a type of novel genome editing technology, signaling an innovative advancement in the field of gene therapy. 

 

“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”

 

This is a game-changer, friends! Not only for sickle-cell patients, but this technology is being developed to cure a number of genetic diseases, including Cystic Fibrosis, for which there has been no cure (only symptom treatment/management strategies) so far.

 

If anyone is interested, these podcast episodes (I understand NPR is not a favorite here, but this is science not politics, so no harm done) are well worth the listen. They document the journey of Mrs. Victoria Gray, who was suffering from the debilitating symptoms of sickle-cell anemia and volunteered as a clinical-trial subject, eventually becoming one of the first (maybe even the first) patients to be cured using this new technology. It is heart-warming and gives hope for the future of science-based medicine advances in improving many lives!

 

https://www.npr.org/sections/health-shots/2019/12/25/784395525/a-young-mississippi-womans-journey-through-a-pioneering-gene-editing-experiment

https://www.npr.org/sections/health-shots/2020/12/15/944184405/1st-patients-to-get-crispr-gene-editing-treatment-continue-to-thrive

 

The caveat is that it is still very expensive and access is an issue, but we are better off with it than without. The science is there, we can figure out the details now!

Edited April 12 by BacktoCricaddict

[gattaca]

Question is what are the side effects of editing. Does it change behavior of a person ? The way they think act. Does this go to designer babies ? You know the last person who wanted it had to kill himself. Nature rejects anything that is unstable. Now people with edited genes will be roaming and procreating what are the long term effects of this ? 

Edited March 13 by gattaca

[BacktoCricaddict]

37 minutes ago, gattaca said:

Question is what are the side effects of editing. Does it change behavior of a person ? The way they think act. Does this go to designer babies ? You know the last person who wanted it had to kill himself. Nature rejects anything that is unstable. Now people with edited genes will be roaming and procreating what are the long term effects of this ? 

 

The entire person is not gene-edited. In the case of sickle-cell anemia, the patient's blood-producing (called hematopoietic) cells are removed, edited to correct one specific sequence and reinserted into the person's cleaned-out bone marrow. Once they take hold, these new cells will produce blood cells with the properly functioning gene. There is no question of affecting anyone's behavior. If you gene-edited someones neurons, yes, there may be complex psychological effects.

 

Yes, there is a danger of people wanting designer babies and such. I view it like AI - there is nothing wrong with the technology itself. It's human malice that can lead to misuse of the technology and guardrails are key.

 

I am not aware of anyone committing suicide because of gene editing. Link?

 

"Mother" Nature does not do anything to restore "stability" in any given species. It has no intent to do anything. If that was the case, how would "she" accept surgical alterations, stents, pacemakers, IVF babies, C-sections, brain-chips inserted to operate computers, prosthetics etc. etc.?  We are in an age where fetal surgeries to correct heart defects are routine!!  And that is just brilliant stuff.

 

The advent of new technologies always evokes fear, but we are better off making progress than not. 

[BacktoCricaddict]

Here's another example. It's a few years old and am not sure of the FDA approval status, but it is promising nonetheless.

 

https://www.science.org/content/article/crispr-helps-blind-woman-see-doesn-t-help-all-patients

 

Quote

The world’s first attempt to use the CRISPR gene-editing tool to treat blindness is showing hints of success, researchers reported today at a vision conference. Of six people who received the therapy starting in March 2020, two can now better sense light, and one of those can now navigate a maze in dim light.

The clinical trial, sponsored by biotech company Editas Medicine, was the first to inject CRISPR’s machinery directly into the body to edit DNA, versus modifying patient cells in a dish and reinfusing them later. The “modest and preliminary” indication that the treatment could help is “really exciting,” says Jacque Duncan, an ophthalmology researcher at the University of California, San Francisco, who chaired the session where the results were presented.

 

Trial participants have Leber congenital amaurosis (LCA), a disease in which genetic defects in the retina’s light-sensing photoreceptor cells or nearby cells cause patients to start to lose their sight in childhood. By adulthood, they may only see dim, blurry images directly in front of them, almost like looking through a drinking straw. Their eyes often wobble from side to side.

 

A gene therapy approved in 2017 for LCA uses a harmless adeno-associated virus (AAV), to deliver a working copy of a gene called RPE65 into retinal cells. But inserting a gene with AAV would not work for the most common form of the disease, LCA type 10 (LCA10). That condition is caused by defects in another gene, CEP290, which encodes for a protein that helps shuttle other proteins around photoreceptor cells. Unfortunately, CEP290 is too large to fit into an AAV virus.

 

So Editas is using an AAV to transport CRISPR’s genetic scissors into retinal cells, instead. Once the DNA for CRISPR’s Cas9 genome-cutting enzyme and two guide RNAs is inside, the cells produce Cas9, which snips out a common mutation in CEP290, allowing it to produce functioning protein.

 

In the trial results released today, six adults who had severely impaired vision got injections of the treatment, EDIT-101, in one eye, in one of three possible doses. For those who had side effects, they were mild, including eye pain or inflammation.

Of the five patients whose vision test results are available, three have not made clear gains. But two, both of whom received the midrange dose, could sense more light than they could before the treatment, as measured by their responses to a flashing light. Investigator Mark Pennesi, a vision science researcher at Oregon Health & Science University, presented the results today at the International Symposium on Retinal Degeneration in Nashville, Tennessee.

 

In addition to the overall results, he said, one of the patients who could sense more light—a 54-year-old woman—also improved significantly on tests of visual acuity 6 months after the treatment. In effect, she went from not being able to read the E at the top of an eye chart to seeing it, Pennesi says. She also mastered an obstacle course in dim light that she had previously failed in bright light. The patient, Carlene Knight of Portland, Oregon, told NPR she no longer bumps into her co-workers’ cubicles. "It’s nice. I don’t scare people and I don’t have as many bruises on my body,” she joked.

 

[BacktoCricaddict]

@gattaca As optimistic as I sound in my posts, things like this make me take pause.

 

https://globalgenes.org/raredaily/death-in-n-of-1-trial-attributed-to-immune-response-to-vector/

Quote

Terry Horgan, the brother of Cure Rare Disease Founder and President Rich Horgan, died from an innate immune response to the vector used in an experimental CRISPR gene therapy the company developed to treat his form of Duchenne muscular dystrophy.

 

The experimental therapy was designed to help Terry Horgan make the muscle protein (full-length dystrophin) that his body is missing. Known as CRISPR transactivation, the therapy was designed to upregulate an alternate form (brain isoform) of the dystrophin protein with the goal of stabilizing symptom progression of Duchenne muscular dystrophy. This is the first time that this new CRISPR approach has been studied in human.

In October 2022, Terry Horgan received an experimental CRISPR gene therapy as the only patient in a clinical study to evaluate a therapy tailored to treat the gene mutation underlying his Duchenne muscular dystrophy.

 

Prior to dosing, the protocol began with suppressing his immune system to prepare his body to receive the therapy, which was delivered with a high dose adeno-associated viral vector for body-wide distribution to his skeletal and cardiac muscles.

Six days after receiving the therapy, his health began to rapidly decline as he showed signs of cardiac and respiratory distress. The post-mortem findings from the study revealed that his lungs had sustained injury likely due to a strong immune reaction to the high dose AAV, and that the gene therapy itself did not have a chance to do what it was designed to do.

 

Cure Rare Disease said Terry was weak and significantly compromised by the disease. He was 27 and it was known that this type of reaction to the vector was a risk given his advanced disease. Nevertheless, he felt that the potential benefit of the therapeutic outweighed the risk.

 

 

 

[Tillu]

I first heard about gene editing and sickle anemia from the book "The Code breaker" about the life of one of the early pioneers of gene editing and Nobel laureate Jennifer Doudna.

 

I read SCA is highly prevalent among Africans. The book also covers the Chinese scientist who first used gene editing to remove Hiv infection among 3 babies. At that time there was big hue and cry about the ethics of using gene editing. He was jailed in China for 3 years and was back to doing his research again.

 

Hope they use this tool for eliminating diseases than creating designer babies.

Edited March 14 by Tillu

[BacktoCricaddict]

8 hours ago, Tillu said:

I first heard about gene editing and sickle anemia from the book "The Code breaker" about the life of one of the early pioneers of gene editing and Nobel laureate Jennifer Doudna.

 

I read SCA is highly prevalent among Africans. The book also covers the Chinese scientist who first used gene editing to remove Hiv infection among 3 babies. At that time there was big hue and cry about the ethics of using gene editing. He was jailed in China for 3 years and was back to doing his research again.

 

Hope they use this tool for eliminating diseases than creating designer babies.

 

SCA persisted in African populations because it gives resistance to malaria. So, during malaria outbreaks, SC carriers were more likely to survive and pass the SC gene variant on to their next generations. Same thing with Cystic fibrosis and cholera.

------------------------------------------------------------

The issue with the Chinese scientist Dr. He was the he was editing IVF embryos in which he was trying to silence a gene. Without this gene, HIV would not be able to bind to the cells of the individual that emerges from this embryo thus making them resistant. According to the Chinese government there was not enough evidence of the safety of gene editing (this was in 2018?) and it had not been approved for mainstream work.

 

Embryo gene editing is a particularly vexing ethical issue because it opens the doors to designer babies. Editing individual genes in independent individuals, on the other hand, is much more controllable and streamlined.

[Tillu]

24 minutes ago, BacktoCricaddict said:

 

SCA persisted in African populations because it gives resistance to malaria. So, during malaria outbreaks, SC carriers were more likely to survive and pass the SC gene variant on to their next generations. Same thing with Cystic fibrosis and cholera.

------------------------------------------------------------

The issue with the Chinese scientist Dr. He was the he was editing IVF embryos in which he was trying to silence a gene. Without this gene, HIV would not be able to bind to the cells of the individual that emerges from this embryo thus making them resistant. According to the Chinese government there was not enough evidence of the safety of gene editing (this was in 2018?) and it had not been approved for mainstream work.

 

Embryo gene editing is a particularly vexing ethical issue because it opens the doors to designer babies. Editing individual genes in independent individuals, on the other hand, is much more controllable and streamlined.

 

Since Malaria is very much prevalent in the Subcontinent and other tropical countries, are we also susceptible to Sickle cell Anemia.

[BacktoCricaddict]

53 minutes ago, Tillu said:

 

Since Malaria is very much prevalent in the Subcontinent and other tropical countries, are we also susceptible to Sickle cell Anemia.

 

Great question! And yes, a sickle cell mutation (a different mutation from the African ones) is also present in high numbers in some tribal Indian populations.

 

These SC mutations did not arise "as a response" to malaria. Instead, they are random mutations that, by random chance, give resistance to malaria whenever there is a malaria outbreak.

 

So, whenever there is a malaria outbreak in places where treatment is not available, the non-SC people may die off due to malaria, but those who had a single copy of the SC mutation would survive it in greater proportions and pass the SC mutation was passed on to future generations.

 

 

[Haarkarjeetgaye]

Can this also work for thalasemia 

[Real McCoy]

On 3/13/2024 at 8:18 PM, gattaca said:

Question is what are the side effects of editing. Does it change behavior of a person ? The way they think act. Does this go to designer babies ? You know the last person who wanted it had to kill himself. Nature rejects anything that is unstable. Now people with edited genes will be roaming and procreating what are the long term effects of this ? 

You are probably the only right thinking poster in this topic. You nailed the post and killed it right there with "Nature rejects anything that is unstable." but our "friend" here will do more topics on its post mortem. Sickle cell anemia is a rather unknown disease for South Asians. I dont know why this dude is pushing these fancy diseases to us like he did corona. CRISPR is bleeding edge "science" and gene editing is dodgy AF.

Even in India, its always better to take a second opinion on big surgeries / operations. If you live in the west, its better not take an opinion at all. Doctors have become pill pushers. There are only a few doctors who buck the system everyone is just following the herd to pay their bills. On top of that, this guy wants you to take a look at gene editing from these hacks 

[BacktoCricaddict]

16 hours ago, Haarkarjeetgaye said:

Can this also work for thalasemia 

Yes, CRISPR-based gene editing therapies for beta thalassemia have also been approved by the FDA (as of Jan 2024).

 

Unfortunately, the cost for gene-editing based cures is highly prohibitive. Part of the reason is that it is not a medication that can be mass-manufactured. It is customized for each patient. Unless this becomes routine enough that costs come down significantly, such treatments are out of the reach of most people.

 

Science rocks!! But economic realities are the main obstacle.

 

 

 

 

 

 

Edited March 15 by BacktoCricaddict

[jf1gp_1]

what we need is cure for diabetes. 

[gattaca]

On 3/13/2024 at 11:37 AM, BacktoCricaddict said:

 

The entire person is not gene-edited. In the case of sickle-cell anemia, the patient's blood-producing (called hematopoietic) cells are removed, edited to correct one specific sequence and reinserted into the person's cleaned-out bone marrow. Once they take hold, these new cells will produce blood cells with the properly functioning gene. There is no question of affecting anyone's behavior. If you gene-edited someones neurons, yes, there may be complex psychological effects.

 

Yes, there is a danger of people wanting designer babies and such. I view it like AI - there is nothing wrong with the technology itself. It's human malice that can lead to misuse of the technology and guardrails are key.

 

I am not aware of anyone committing suicide because of gene editing. Link?

 

"Mother" Nature does not do anything to restore "stability" in any given species. It has no intent to do anything. If that was the case, how would "she" accept surgical alterations, stents, pacemakers, IVF babies, C-sections, brain-chips inserted to operate computers, prosthetics etc. etc.?  We are in an age where fetal surgeries to correct heart defects are routine!!  And that is just brilliant stuff.

 

The advent of new technologies always evokes fear, but we are better off making progress than not. 

Human body has over 100 trillion cells. Bone marrow it self produces over billions of cells every day. Are they going to catch cells with bad DNA in billions of cells in marrow ? But the question arises why do humans have bad DNA cells. I am assuming they get it at  birth or mutations later? Mutations can happen anytime. There would be remission in these patients as well. Still feels like finding something in ocean. Stunts , c sectional , pacemakers are not at a cell level. This is changing the building blocks of human body. 

Edited March 16 by gattaca

[gattaca]

2 hours ago, jf1gp_1 said:

what we need is cure for diabetes. 

We do have cure. No rice or sugar based diets.  Balanced diets is something long gone. Our gut has lower and lower bacteria compared to our ancestors who ate balanced diets and didn’t eat every day. The more bad bacteria we breed they crave for more sugars eventually it will be bad for us.

Edited March 16 by gattaca

[jf1gp_1]

1 hour ago, gattaca said:

We do have cure. No rice or sugar based diets.  Balanced diets is something long gone. Our gut has lower and lower bacteria compared to our ancestors who ate balanced diets and didn’t eat every day. The more bad bacteria we breed they crave for more sugars eventually it will be bad for us.

that's lifestyle change not cure.  

[Vijy]

13 hours ago, jf1gp_1 said:

that's lifestyle change not cure.  

there are an array of studies being conducted on rats, etc. none can be deemed as cures yet, though

[Tillu]

Ignore the naysayers and a few luddites on this forum. Keep posting the groundbreaking research happening in the medical world.

[gattaca]

18 hours ago, Tillu said:

Ignore the naysayers and a few luddites on this forum. Keep posting the groundbreaking research happening in the medical world.

The same ideology was used to push Covid vaccine. People were called all kind of names for not taking it or lost jobs. Can’t people question medical world ? Is medical world above everyone ? Medical world wrote their own rules and regulate themselves and pharmaceutical world is smart they used same McKinsey consulting as FDA to get medicines approved. Pharma companies got meth approved as medicine and opioids as well.

Edited March 20 by gattaca

[Tillu]

2 hours ago, gattaca said:

The same ideology was used to push Covid vaccine. People were called all kind of names for not taking it or lost jobs. Can’t people question medical world ? Is medical world above everyone ? Medical world wrote their own rules and regulate themselves and pharmaceutical world is smart they used same McKinsey consulting as FDA to get medicines approved. Pharma companies got meth approved as medicine and opioids as well.

 

As with any industry there will be discrepancies and corrupt practices coming into light every now and then.

 

If doubting Thomases had their way we'll be still dieing and suffering from Malaria, Tuberculosis, Hepatitis, Polio etc.

 

Just within the last 100 years average life span has increased from 30 to 70 years world over. Infant mortality rates and maternal mortality rates have greatly plummeted.

 

The benefits of the medical research far outweigh whatever minor disadvantages we see. Yes we should have a sceptical mind with everything. But instead of ridiculing the poster be a little respectful.

Edited March 21 by Tillu