I have an extremely rare autosomal dominant subtype of a certain genetic disorder that affects maybe less than a few thousand individuals at any one time in the USA. Much common versions of the disorder that affect children have been successfully treated/cured with gene therapy. However gene treatment unlikely to ever reach people like me because so few are affected by it, it's not viable commercially. It's extremely frustrating and I struggle with tremendous feelings of anger about it, but I can't really do anything short of become a billionaire and fund my own treatment. Such is the state of medicine for profit, I guess.
The fact that for profit medicine is holding up some of the most advanced medical treatments in history is really disturbing. As a society, there will be a significant benefit, especially once it's cost optimized. But we'll never get there if beancounters hold it up, preferring short term profits above all else.
I'd love to know if anyone knows what a solution to this problem might look like.
Even with 100% public healthcare system you have budget constraints. What’s better to provide one treatment for a rare gene decease or cure 10 cancer patients?
To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases.
That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this science long-term? Consider a cure for the common cold. All of the technology exists. We can take a tissue or fluid sample and extract viral genomes, comparing against a database of over 100k viruses. We can develop MRNA vaccines that target specific viral proteins. We can do both of these things using current technology in a timeframe of less than a day.
To me this is the next great leap. Gene therapy is less a technology problem than it is an infrastructure problem, and rare diseases cannot support the infrastructure. But there are plenty of wealthy people who would pay $10k, maybe even $50k, out of pocket to cancel a cold. Rare diseases bootstrapped the tech, common diseases can scale it, and once scaled, everyone benefits.
From what I understand the situation is quite the opposite, there is a huge pipeline of investment both in startups as well as very large corps on the development and application of gene therapy.
As anecdata, Luxturna costs north of a quarter of a million per vial, it treats a fairly rare disease (Leber congenital amaurosis). Roche still poured millions into development.
Bio-tech, specially in a Medical field, is a very difficult business. The strategy for must startups is to get bought by a very large pharma company. The issue is that these companies often run out of runway, specially when dealing with later pre-clinical, clinical, and regulatory costs.
Could it be just that gene therapies should be publicly funded?
Taxpayer money has paid for a substantial percentage of research around the world, and it doesn't seem necessary that we rely on profit-driven private companies for the actual therapies when they could be done at publicly funded hospitals too.
It's less the research and more getting a treatment to people. Governments around the world refuse to pay for this, and in fact demand that various risks and expenses be paid by pharma companies, with mostly negative results.
It is so bad that for a lot of treatments, getting them to people costs upwards of hundreds of millions of dollars. And almost all of these efforts fail.
This would mean the government would need to breed (and pay for) lab animals, small and large (from mice to primates). Would need to pay more for medical care, would need to collect (and pay) people to try out experimental drugs and treatments on. If these treatments or drugs have adverse effects, the government would need to shoulder sometimes lifelong payments and care to these people. It would need to cover all this knowing that in 90% or so of cases the whole effort was for nothing.
I had hemophilia gene therapy. It worked for a period of time but the results were not permanent. The problem with many of the gene therapies is that they do not change the nuclear DNA, they just insert copies of working genes into the cell. If a cell dies, it’s gone. The results aren’t carried through to new cells during division.
The other problem is with viral vector based gene therapy is you can’t have it again. You develop antibodies which prevent it from working again, and it could cause a dangerous immune response.
Then there’s the cost. My single treatment cost $3 million as part of a clinical trial, and lasted about 3 years. Normally, it costs about $1 million a year for my normal factor product, which I had to go back on. So I guess it was a wash and it was nice to be free of the medication for a few years. But it’s definitely not perfect and has its own limitations.
I am sorry you experience this disease. I have a question: You said "they do not change the nuclear DNA, they just insert copies of working genes into the cell ... The results aren’t carried through to new cells during division."
Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene?
I can imagine other cases, for example, progenitor cells were not infected, cells that do not divide, etc...
AAV-based vectors are specifically non-integrating. Wild-type AAVs can integrate, but in the absence of rep protein they will instead persist in the cell nucleus in the form of episomal concatemers - long, circular DNA structures containing multiple copies of the virus DNA. These will not replicate when a cell proliferates - they will instead dilute with each division. This makes them desirable for treating diseases affecting post-mitotic tissue like muscle, less so for, say, bone marrow. Unless transient expression (but not as transient as with NLPs) is what you want.
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[ 3.0 ms ] story [ 45.0 ms ] threadI'd love to know if anyone knows what a solution to this problem might look like.
That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this science long-term? Consider a cure for the common cold. All of the technology exists. We can take a tissue or fluid sample and extract viral genomes, comparing against a database of over 100k viruses. We can develop MRNA vaccines that target specific viral proteins. We can do both of these things using current technology in a timeframe of less than a day.
To me this is the next great leap. Gene therapy is less a technology problem than it is an infrastructure problem, and rare diseases cannot support the infrastructure. But there are plenty of wealthy people who would pay $10k, maybe even $50k, out of pocket to cancel a cold. Rare diseases bootstrapped the tech, common diseases can scale it, and once scaled, everyone benefits.
As anecdata, Luxturna costs north of a quarter of a million per vial, it treats a fairly rare disease (Leber congenital amaurosis). Roche still poured millions into development.
Bio-tech, specially in a Medical field, is a very difficult business. The strategy for must startups is to get bought by a very large pharma company. The issue is that these companies often run out of runway, specially when dealing with later pre-clinical, clinical, and regulatory costs.
Taxpayer money has paid for a substantial percentage of research around the world, and it doesn't seem necessary that we rely on profit-driven private companies for the actual therapies when they could be done at publicly funded hospitals too.
It is so bad that for a lot of treatments, getting them to people costs upwards of hundreds of millions of dollars. And almost all of these efforts fail.
This would mean the government would need to breed (and pay for) lab animals, small and large (from mice to primates). Would need to pay more for medical care, would need to collect (and pay) people to try out experimental drugs and treatments on. If these treatments or drugs have adverse effects, the government would need to shoulder sometimes lifelong payments and care to these people. It would need to cover all this knowing that in 90% or so of cases the whole effort was for nothing.
This is, to put it mildly, not happening.
It’s pretty rare, but there is gene therapy in the works promising 2027 timeline or so for availability.
The other problem is with viral vector based gene therapy is you can’t have it again. You develop antibodies which prevent it from working again, and it could cause a dangerous immune response.
Then there’s the cost. My single treatment cost $3 million as part of a clinical trial, and lasted about 3 years. Normally, it costs about $1 million a year for my normal factor product, which I had to go back on. So I guess it was a wash and it was nice to be free of the medication for a few years. But it’s definitely not perfect and has its own limitations.
Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene?
I can imagine other cases, for example, progenitor cells were not infected, cells that do not divide, etc...
Thanks for any answer