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Gene Therapy

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Gene Therapy

Old 29th Jan 2020, 07:13
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Gene Therapy

Rather than another specific thread, such as that on blindness cures, I thought I’d start a generic one, since various cures now seem to be being announced at regular intervals....

https://medicalxpress.com/news/2020-...ease-gene.html

Six patients with rare blood disease are doing well after gene therapy clinical trial

UCLA researchers are part of an international team that reported the use of a stem cell gene therapy to treat nine people with the rare, inherited blood disease known as X-linked chronic granulomatous disease, or X-CGD. Six of those patients are now in remission and have stopped other treatments. Before now, people with X-CGD—which causes recurrent infections, prolonged hospitalizations for treatment, and a shortened lifespan—had to rely on bone marrow donations for a chance at remission......

People with chronic granulomatous disease, or CGD, have a genetic mutation in one of five genes that help white blood cells attack and destroy bacteria and fungus using a burst of chemicals. Without this defensive chemical burst, patients with the disease are much more susceptible to infections than most people. The infections can be severe to life-threatening, including infections of the skin or bone and abscesses in organs such as lungs, liver or brain. The most common form of CGD is a subtype called X-CGD, which affects only males and is caused by a mutation in a gene found on the X-chromosome.

Other than treating infections as they occur and taking rotating courses of preventive antibiotics, the only treatment option for people with CGD is to receive a bone marrow transplant from a healthy matched donor. Bone marrow contains stem cells called hematopoietic, or blood-forming, stem cells, which produce white blood cells. Bone marrow from a healthy donor can produce functioning white blood cells that effectively ward off infection. But it can be difficult to identify a healthy matched bone marrow donor and the recovery from the transplant can have complications such as graft versus host disease, and risks of infection and transplant rejection........

In the new approach, Kohn teamed up with collaborators at the United Kingdom's National Health Service, France-based Genethon, the U.S. National Institute of Allergy and Infectious Diseases at the National Institutes of Health, and Boston Children's Hospital. The researchers removed hematopoietic stem cells from X-CGD patients and modified the cells in the laboratory to correct the genetic mutation. Then, the patients' own genetically modified stem cells—now healthy and able to produce white blood cells that can make the immune-boosting burst of chemicals—were transplanted back into their own bodies. While the approach is new in X-CGD, Kohn previously pioneered a similar stem cell gene therapy to effectively cure a form of severe combined immune deficiency (also known as bubble baby disease) in more than 50 babies.

The viral delivery system for the X-CGD gene therapy was developed and fine-tuned by Professor Adrian Thrasher's team at Great Ormond Street Hospital, or GOSH, in London, who collaborated with Kohn. The patients ranged in age from 2 to 27 years old; four were treated at GOSH and five were treated in the U.S., including one patient at UCLA Health.

Two people in the new study died within three months of receiving the treatment due to severe infections that they had already been battling before gene therapy. The seven surviving patients were followed for 12 to 36 months after receiving the stem cell gene therapy. All remained free of new CGD-related infections, and six of the seven have been able to discontinue their usual preventive antibiotics. “None of the patients had complications that you might normally see from donor cells and the results were as good as you'd get from a donor transplant—or better," Kohn said.

An additional four patients have been treated since the new paper was written; all are currently free of new CGD-related infections and no complications have arisen........

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Old 19th Nov 2020, 05:23
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https://medicalxpress.com/news/2020-...nt-cancer.html

Revolutionary CRISPR-based genome editing system treatment destroys cancer cells

......"It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell's DNA, thereby neutralizing it and permanently preventing replication.".....
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Old 19th Nov 2020, 08:21
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Originally Posted by ORAC View Post
https://medicalxpress.com/news/2020-...nt-cancer.html

Revolutionary CRISPR-based genome editing system treatment destroys cancer cells

......"It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell's DNA, thereby neutralizing it and permanently preventing replication.".....
There are some very cool new anti viral therapies under development that use the same principle. In fact, that is what the Cas9 system evolved to do. You could even 'engineer-in' permanent and heritable resistance to specific viruses (or tumors), and I predict that will be done in animals, probably a bit more contentious in humans.
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Old 25th Dec 2020, 06:03
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https://www.thetimes.co.uk/article/g...ease-3pwp023vl

Gene editing cures sickle cell disease

A revolutionary gene-editing tool has been used to treat an inherited disease for the first time, producing results that experts described as “unbelievably exciting”.

Victoria Gray, 34, had sickle cell disease (SCD), a debilitating condition in which red blood cells, which should be circular, became rigid and sticky and adopted a crescent shape.

These misshapen cells can clog blood vessels and damage organs, causing intense pain. On adverage Ms Gray, a mother of four who lives in Mississippi, had been experiencing one of these episodes, known as crisis events, every couple of months. After the gene-editing treatment, which involved editing the DNA of stem cells taken from her bone marrow, she has been free of them for more than a year.

Helen O’Neill, a lecturer in molecular genetics and an expert in genome editing at University College London who was not involved in the trial, said that the results were “unbelievably exciting”.

It had been possible to modify the genetic code inside a person’s own cells to restore a critical function”, she said. “We’re on the cusp, a crisis-free life for people with sickle cell is on the horizon.”......

The studies mark the first time that Crispr-Cas9 has been used to treat, and potentially cure, a disease. Alena Pance, senior staff scientist at the Wellcome Trust Sanger Institute, said: “These developments are super exciting. These are the first efforts to use genome editing technologies to overcome inherited diseases for which there are no cures.

“These trials serve not only as concrete medical strategies that are providing treatment to patients but also as proof of principle that genome editing applications in humans are possible and successful. What is amazing about these studies is that these approaches are becoming increasing real or even normal rather than isolated medical ideas looked at with suspicion.”.....

The studies mark the first time that Crispr-Cas9 has been used to treat, and potentially cure, a disease. Alena Pance, senior staff scientist at the Wellcome Trust Sanger Institute, said: “These developments are super exciting. These are the first efforts to use genome editing technologies to overcome inherited diseases for which there are no cures.

“These trials serve not only as concrete medical strategies that are providing treatment to patients but also as proof of principle that genome editing applications in humans are possible and successful. What is amazing about these studies is that these approaches are becoming increasing real or even normal rather than isolated medical ideas looked at with suspicion.”......

John Parrington, lecturer in cellular and molecular pharmacology at the University of Oxford, said that other diseases caused by a single faulty mutation may potentially be treatable using similar approaches. They include muscular dystrophy, which gradually cause the muscles to weaken, leading to an increasing level of disability, and Huntington’s disease, a condition that stops parts of the brain working properly over time.......
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Old 10th Apr 2021, 06:33
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https://phys.org/news/2021-04-revers...nderlying.html

New, reversible CRISPR method can control gene expression while leaving underlying DNA sequence unchanged

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Old 29th Apr 2021, 21:40
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https://www.bbc.co.uk/news/health-56906002

Gene therapy: 'Now I can see my own face again'

Jake Ternent has been gradually losing his central vision since birth, because of a rare inherited genetic eye condition.

And, despite the pandemic, 2020 was a landmark year for the 24-year-old, from County Durham, who became the first person in the UK to receive a revolutionary new gene therapy on the NHS.

"It was science fiction, about a year-and a half ago, to think that my eyesight could improve at all," Jake told the BBC.

His condition - leber congenital amaurosis (LCA) - is caused by having two faulty copies of a gene called RPE65, which is essential for maintaining healthy photoreceptor cells in the retina.

In 2019 the NHS agreed to fund the treatment, Luxturna, the first in a new generation of gene therapies for conditions causing blindness. It costs about 600,000 per patient to treat both eyes, though the NHS has agreed a confidential discount with the makers Novartis.

About 100 people in the UK are likely to be eligible for the gene therapy, which is being carried out at four hospitals in England.

Jake underwent the procedure, which is intended to halt further sight loss, at London's Moorfields Eye Hospital in January last year.

Jake says that not only has it stabilised the sight in his right eye, it also appears to have reversed some of the decline in vision he has experienced in recent years....
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Old 30th Apr 2021, 05:22
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There is little doubt that gene-editing therapies are the future, especially for cancers whose present treatment involves often gruelling chemotherapy, or radiotherapy that can cause as many issues as they solve. That said, with CRISPR technology 'we' are beginning to play God with our species and adjacent species. Already there have been mentions of less concerned docters and scientists genetically altering in-vitro healthy foetuses to have, or not have certain characteristics. Then we have the malevolent manipulation of genes unbeknown to the recipient to bring about a demise, a gene warfare if you will with no shots fired.

Gene-editing is a game changer, no doubt about it, I just hope that it doesn't bring about a two-tier health system.
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Old 30th Apr 2021, 07:00
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100 people x 600,000 a pair (60,000,000) is a lot of bread - while I believe that everyone should have access to treatment for these rare diseases, why did Novartis think the NHS would fund this, even if it is an undisclosed amount?

Novartis must be well in with the NHS for them to divvy up this amount of money.

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Old 30th Apr 2021, 07:22
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Adverum Biotechnologies…announced a Suspected Unexpected Serious Adverse Reaction (SUSAR) of hypotony (clinically-relevant decrease in ocular pressure) in its INFINITY clinical trial evaluating ADVM-022 gene therapy for the treatment of diabetic macular edema (DME). This event occurred 30 weeks after randomization in one patient treated with a single intravitreal injection of the high dose (6 x 10^11 vg/eye) of ADVM-022 who has developed hypotony, with panuveitis and loss of vision in the treated eye.

In the interests of patient safety, Adverum has decided to immediately unmask the INFINITY Phase 2 study to better understand this event and to help identify and manage any similar potential risk to other patients in this study, which completed patient dosing in December 2020. Additionally, the company is conducting a thorough review of data from the ADVM-022 program and plans to report its findings as the analysis progresses.
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Old 30th Apr 2021, 07:43
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100 people x 600,000 a pair (60,000,000) is a lot of bread - while I believe that everyone should have access to treatment for these rare diseases, why did Novartis think the NHS would fund this, even if it is an undisclosed amount?
Such things are funded as trials to explore the technology and the benefits. Administered at an early stage the treatment could obviate the need for a lifetime of treatment and support far outweighing the cost of the original therapy.
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Old 30th Apr 2021, 18:32
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There really is a lot starting to happen. Someone close is a 15 year-old with Stargardt's but now knows that the possibilities for cure or stabilisation are growing all the time.
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Old 30th Apr 2021, 23:17
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I'm stating the obvious but it's the science we're funding. The wonderful gift to the recipients is akin to a by-product.

I've had a vitrectomy followed by a self funded cataract in Texas. A decade or more later I had a vitrectomy and peel with the inevitable cataract later. When the main operation had stabilised, my eyesight was fabulous. It's a shame the cataract gets triggered by the op.

I was shattered when I had a bleed in my eye. I knew nothing of vitrectomy procedures and the big blob on centre vision was horrible.

Anyway, the point is I'm profoundly grateful for these ops, they let me carry on with a normal life, including fettling watches.

Darn dry eyes are troubling me now, but that may be the months of being stuck indoors. Tears are just another miracle, as many as 7 layers of chemistry. Impossible to truly replicate.
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Old 1st May 2021, 00:42
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Some forms of gene therapy will continue too be extremely expensive for the foreseeable future.

The thing about the future is that we cannot foresee everything, so the first steps into unknown territory let others stand on the shoulders of giants, or at least move it another small step forward towards a more realistic goal.

To quote Star Trek:
”To boldly go where no man has gone before.”
Doesn’t mean you know where you are going, nor the best way to get there. It probably means at least learning as you go along to the best of your ability and doing your best to learn from past mistakes.

It is called experimental medicine for a reason.

The mechanics of flying that the Wright Brothers faced when learning to fly are pretty simplistic in comparison to understanding the mechanics of how the human body works.

Learning to tweak the latter to correct every ailment is very difficult, especially as we don’t even know every which way that things can go wrong, nor how problems can be interconnected.
———-
The NHS does put a cap on money spent per patient per years of life saved, if I understand it correctly, so they do draw the line at some treatments.

If you have deep pockets, these constraints may not apply.

Last edited by visibility3miles; 1st May 2021 at 00:54.
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Old 1st May 2021, 04:42
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An important message is that such treatments emerge from a solid foundation of hard science. Often abstract and not obviously applicable science. Scientists almost never talk about "breakthroughs", it's a steady progression and a pulling together of a mix of different advances.

The COVID vaccines are the perfect example, many people are asking how it's possible to make a vaccine to a new virus so fast. But it builds on decades of vaccinolgy. Lots of people with a crazy mishmash of funding doing hard work to build basic capabilities. Much of it really not sexy science: building algorithms to identify target epitopes, tweaking screening systems, small improvements in sequencing, etc.

I really hope that message gets across to the governments, public and funders who are too often obsessed with seeing tangible, short-term impacts from this week's investment.

Last edited by double_barrel; 1st May 2021 at 05:08.
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Old 1st May 2021, 13:33
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Can someone explain why the retail costs of gene therapy are so immense per patient ? Obviously the development of the techniques are large amd time consuming over years, but once a proven technique has been developed, surely (in simple terms) you harvest the patient's DNA and remove/add the affected strands using the CRISPR or similar methods and then support the patient until a hopefully successful conclusion ?
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Old 1st May 2021, 13:59
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Can someone explain why the retail costs of gene therapy are so immense per patient ?
The cost of trials is immense (in the $Bs) whilst the conditions fir which they are specifically designed affect only a few dozen or hundreds of people compared to the millions for more common diseases - therefore the costs have to be high to recover the development costs.

The other options are public ally funded therapies and trials or the companies stopping work on producing new therapies because they aren’t commercially viable.

https://fee.org/articles/why-this-ne...ts-21-million/
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Old 2nd May 2021, 00:49
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Can someone explain why the retail costs of gene therapy are so immense per patient ?
There are forms of gene therapy, such as some used to create chimeric-T cells (CAR-T) to treat cancer, where you harvest immune cells from a patient, as in one single individual, treat it in some way to introduce a chimeric antigen receptor (CAR) that is designed to recognize that person’s cancer, then after the new gene has been introduced into their cells, you grow that persons cells in an incubator until you have a lot more of them, then you put them back into that person and hope the artificial receptor that you introduced will recognize and bind to the cancer, allowing those immune system cells to kick into gear and kill the cancer target.

This is is a lot of work done under extremely sterile conditions by a lot of people to treat one patient.

This type of gene therapy is not a one size fits all, pill in a bottle, approach, although it can work miracles. Or fail for any number of reasons.

Other types of gene therapy are more generic, such as introducing something, often a highly modified virus, into say someone’s eyeball, which is a very localized space, which can provide a necessary gene to make a protein of some sort that the person lacks, thereby correcting the original problem.
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Old 11th May 2021, 19:58
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https://www.thetimes.co.uk/article/n...bies-t9tk5ckdt

New gene therapy could free ‘bubble boy’ babies

A new gene therapy offers fresh hope of a cure for children with a rare “bubble boy” disease, according to the results of a Great Ormond Street Hospital trial.

The treatment was successful in 48 out of 50 children with the life-threatening disease, with scientists describing their findings as a “game-changer”.

Severe combined immunodeficiency due to adenosine deaminase deficiency, also known as ADA-SCID, is caused by mutations in the gene that creates the enzyme adenosine deaminase, which is essential to a functioning immune system…..

The standard treatment for ADA-SCID involves injections of the ADA enzyme once or twice weekly until a matched bone marrow donor can be found. Untreated, most children with the condition die before their second birthday…..

The new treatment involves removing stem cells that create blood and immune cells from the patient, and then using a viral vector to deliver a new copy of the ADA gene into the cells’ DNA. The corrected cells are then returned to the patient and appear to go on to produce a continual supply of healthy immune cells that can fight off infections…..

The new study, published in the New England Journal of Medicine, also involved teams from the University of California Los Angeles, where ten children were treated using a frozen preparation of corrected stem cells, who did similarly well.….

Dr Claire Booth, co-lead author of the report
said: “If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions, removing the need to find a matched donor for bone marrow transplant and the toxic side effects often associated with that treatment.

“We need and want guidelines to change so we can start offering this potential cure to children and provide it as a first-choice treatment — this research could set those wheels in motion.”

The children were treated in clinical trials between 2012 and 2017. The published paper reports on their status two or three years later, but Booth said the effects had endured and some of her patients were now being transferred to adult services….

Four-year-old Sarah from south Yorkshire was diagnosed with ADA-SCID shortly after birth, after her mother, Maria, became concerned about her daughter’s weight loss and a sore, bleeding nappy rash that wouldn’t heal.

Maria said: “I remember the exact time I saw the paper that had the blood test results and the diagnosis. I saw it was SCID and I was incredibly upset . . . I wasn’t allowed to kiss my daughter or sleep next to her. Everything had to be highly sterilised to keep her safe. It was horrible to not be able to do normal things with my own daughter.”

Several years after gene therapy, she said, her daughter is now doing very well: “Before, her nappy rash was always bleeding and sore, she was being sick and losing weight. Six months after she was given the gene therapy her skin was clean and healthy and the other symptoms got a lot better. She’s doing so well now and can do everything a normal child her age would do.”
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Old 11th May 2021, 20:31
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Didn't they have Gene Editing in Brave New World? ...albeit that they used alcohol instead of Crisper

I remember something about Alphas, Bravos etc, all the way down to the (lowly) Epsilons
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Old 12th May 2021, 05:37
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It's got amazing potential for healing the mistakes of genetic disorders within family lines, but also the potential to be misused by the mistakes of disordered personalities to control the natural order to their desire.
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