Europe to approve gene therapy

[SpaceMarine93]

From BBC News:

http://www.bbc.co.uk/news/health-18926892

Gene therapy nears approval in Europe
By James Gallagher
Health and science reporter, BBC News

Gene therapies alter a patient's DNA
Continue reading the main story
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Europe is on the cusp of approving a gene therapy for the first time, in what would be a landmark moment for the field.

Gene therapies alter a patient's DNA to treat inherited diseases passed from parent to child.

The European Medicines Agency has recommended a therapy for a rare genetic disease which leaves people unable to properly digest fats.

The European Commission will now make the final decision.

The idea of gene therapy is simple: if there is a problem with part of a patient's genetic code then replace the code.

The reality has not been so easy. In one gene therapy trial a US teenager, Jesse Gelsinger, died, and other patients have developed leukaemia.

There no gene therapies available outside of a research lab in Europe or the US.

Gene change
The European Medicines Agency's Committee for Medicinal Products for Human Use has considered the use of Glybera to treat lipoprotein lipase deficiency.

One in a million people have the deficiency. They have damaged copies of a gene which is essential for breaking down fat.

It leads to fat building up in the blood, abdominal pain and life-threatening pancreatitis (inflammation of the pancreas).

The only way to manage the condition is by having a very low-fat diet.

The therapy uses a virus to infect muscle cells with a working copy of the gene.

It was recommended for patients with severe pancreatitis, who cannot control the disease through diet.

'Afraid of a normal meal'

The manufacturer, UniQure, said the decision was a "major breakthrough" for patients and medicine as a whole.

UniQure chief executive officer Jorn Aldag said: "Patients with lipoprotein lipase deficiency are afraid of eating a normal meal because it can lead to acute and extremely painful inflammation of the pancreas, often resulting in a visit to intensive care.

"Now, for the first time, a treatment exists for these patients that not only reduces this risk of getting severely sick, but also has a multi-year beneficial effect after just a single injection.

"Restoring the body's natural ability to break down fat particles in the blood, in order to prevent pancreatitis and excruciating abdominal pain suffered by patients, is what gene therapy is all about: curing disease at the genetic level."

Dr Tomas Salmonson, from the agency's Committee, said the use of Glybera should be restricted to patients "with greatest need".

China was the first country to officially sanction a gene therapy.

[Simon_Jester]

All for it.

I bet we could do this for a lot of things- for example, get all those pink ribbon drives to develop a similar method for BRCA1- which would probably have a lot of knock on effects, and would be a lot more appealing than a double mastectomy as a 'treatment' for the high risk of breast cancer.

[Eternal_Freedom]

Excellent. I would like nothing more than to avoid passing on my shitty eyesight to my kids. This is the first step to that goal.

[Bedlam]

No ones talking about Somatic modification yet so it doesn't stop a genetic condition being passed on to your children just fixes the problem in you.

Somatic modification sounds good but its hard to do and think how long it take to test if there are any problems in 2 generations time.

[Eternal_Freedom]

Still, it's a promising step. If nothing else it means Europe is accepting the idea in principle and more work can be done. It's still promising whether it leads to my hoped-for future or if it doesn't, it's going to help somebody.

[someone_else]

No ones talking about Somatic modification yet so it doesn't stop a genetic condition being passed on to your children just fixes the problem in you.

Theoretically fixing the problem for your offspring should be easier, since you are acting on a single very specific kind of cell in a very limited area of your body (specialized staminal cells for men or ovocytes for wimmins). The issue is that those cells are far better defended than the average muscle cell.

And of course this kind of modification does not cure a damn thing in the patient. IT's still likely a very sought-after procedure anyway.

Besides, it's probably better done on zygotes (less defences and far less stuff that interferes) and then inplant them.

The long-term effects of modern gene therapies are still horribly complex to predict, but when they stop trying to integrate a lenght of DNA ANYWHERE in the genome at random (you see the stupidity of this on your own) and start working with chromosomes (either extract-amplificate-fix-swap-with-the-damaged-one or adding an artificial one with the fix), a lot of the uncertainty should disappear.

[kc8tbe]

No ones talking about Somatic modification yet so it doesn't stop a genetic condition being passed on to your children just fixes the problem in you.

Actually, they are talking about somatic modification. You're thinking of germline modification.

Theoretically fixing the problem for your offspring should be easier...

Not just theoretically, but also in practice. If you know exactly which gene is to blame, you can already use preimplantation genetic diagnosis to avoid passing it on to your offspring in many cases. Present examples include BRCA1 and BRCA2 genes. The trickier part, actually, turns out to be figuring out which gene to target. Myopia and, to name a more medically serious example, endometriosis are both conditions with some heritable component for which we don't know which gene is responsible. The wider availability and lower cost of whole-genome sequencing and bioinformatics will hopefully lead to routine sequencing of individuals for medical research and the identification of such genes.

[Broomstick]

You're forgetting the environmental component for many disorders is arguably just as important as the genetic one. Myopia is very strongly linked to environment, for example. Tribal people living a traditional lifestyle have very low rates of it, but if their children are brought up in a first world environment myopia rates can skyrocket in the younger generation. We should perhaps consider altering the environment for that one before altering our genes.

Other cases, of course, are much more cut-and-dried obvious candidates for a gene fix.

While I applaud the forward progress of science let's not forget that up until now gene therapy trials in humans have had quite mixed results. They aren't entirely without risk.

[Eternal_Freedom]

You're forgetting the environmental component for many disorders is arguably just as important as the genetic one. Myopia is very strongly linked to environment, for example. Tribal people living a traditional lifestyle have very low rates of it, but if their children are brought up in a first world environment myopia rates can skyrocket in the younger generation. We should perhaps consider altering the environment for that one before altering our genes.

Other cases, of course, are much more cut-and-dried obvious candidates for a gene fix.

While I applaud the forward progress of science let's not forget that up until now gene therapy trials in humans have had quite mixed results. They aren't entirely without risk.

In my case it's congential glaucoma, so a genetic fix would be perfect.

[someone_else]

Not just theoretically, but also in practice. If you know exactly which gene is to blame, you can already use preimplantation genetic diagnosis to avoid passing it on to your offspring in many cases.

This assumes that the issue isn't present in ALL of your offpsring like say the case for recessive genes or stuff passed by sexual chromosomes.
Or that it isn't multigenic and that multiple genes on different chromosomes are wrecked (this makes a pretty fun time if the issue is in the mother as the odds are against you).

There are simple cases, and there are HARD ones.

While I applaud the forward progress of science let's not forget that up until now gene therapy trials in humans have had quite mixed results. They aren't entirely without risk.

Most of the issues cam from the usage of horribly inefficient techniques, where your new DNA would go and integrate itself wherever it felt like integrating in the whole genome. It could kill tons of other genes, activate stuff best left dormant, do nothing at all or do too fucking much for every cell it got into, so it's a huge battery of russian roulette.

Chromosome vectors avoid this issue by inserting another tiny chromosome which won't touch the original genome. That's the next bigh thing because of that.
None knows how well it will handle reproduction, but I think they can figure out a way to add genes that force the zygote to rebuild it whole if it was split during meiosis.

[Broomstick]

While I applaud the forward progress of science let's not forget that up until now gene therapy trials in humans have had quite mixed results. They aren't entirely without risk.

Most of the issues cam from the usage of horribly inefficient techniques, where your new DNA would go and integrate itself wherever it felt like integrating in the whole genome. It could kill tons of other genes, activate stuff best left dormant, do nothing at all or do too fucking much for every cell it got into, so it's a huge battery of russian roulette.

True. However, that IS sort of the state of the art at present.

Chromosome vectors avoid this issue by inserting another tiny chromosome which won't touch the original genome. That's the next bigh thing because of that.
None knows how well it will handle reproduction, but I think they can figure out a way to add genes that force the zygote to rebuild it whole if it was split during meiosis.

Or it could result in people who are reproductively sterile outside of artificial means. Or something else. While I think the research is valuable it should proceed with caution because until we do this we don't really know what the short and long term effects will be.

[Memnon]

While I applaud the forward progress of science let's not forget that up until now gene therapy trials in humans have had quite mixed results. They aren't entirely without risk.

Most of the issues cam from the usage of horribly inefficient techniques, where your new DNA would go and integrate itself wherever it felt like integrating in the whole genome. It could kill tons of other genes, activate stuff best left dormant, do nothing at all or do too fucking much for every cell it got into, so it's a huge battery of russian roulette.

True. However, that IS sort of the state of the art at present.

Chromosome vectors avoid this issue by inserting another tiny chromosome which won't touch the original genome. That's the next bigh thing because of that.
None knows how well it will handle reproduction, but I think they can figure out a way to add genes that force the zygote to rebuild it whole if it was split during meiosis.

Or it could result in people who are reproductively sterile outside of artificial means. Or something else. While I think the research is valuable it should proceed with caution because until we do this we don't really know what the short and long term effects will be.

I admit I was skeptical (what if a trisomy happens?), but the article explains it pretty well, especially since they get rid of any endogenous genes and therefore basically get rid of weird gene interactions (that aren't caused by the inserted gene(s) of interest).

Here's the important part in reply:

The SC20-HAC was transmittable through the germline and was rather stable in mice and cattle.13, 15, 16, 17 Both 21ΔqHAC and 21ΔpqHAC were very stable in human cell lines.14, 18, 19

In other words, that's about as good as you're going to get outside of large human trials. Though it's basically very difficult to ensure x copies per cell, it should be stable enough that you can detect them in the germ cells -- or, failing that, in the fetus's genome, which we now can sequence only from the mother's blood. That is, it's likely that normal reproduction would be safe but you would want to get tested just in case. Honestly though, that isn't much worse than being an over 35 mother.

[Broomstick]

This technique hasn't been around long enough to make that comparison.

Women over 35 have been having kids for ... well, since we became human, I imagine. The risks are well known and quantified. Right now we think this sort of gene therapy is relatively low-risk but until it is used multiple times over multiple generations we actually won't know.

[Memnon]

This technique hasn't been around long enough to make that comparison.

Women over 35 have been having kids for ... well, since we became human, I imagine. The risks are well known and quantified. Right now we think this sort of gene therapy is relatively low-risk but until it is used multiple times over multiple generations we actually won't know.

Well, that's why the authors used mice, which have much shorter generation times than do humans. As placental mammals (and fairly close to us, at that), their reproductive systems are very similar to ours in both physical and genetic comparisons. As I said earlier, it's not a substitute for large-scale human trials, but it's definitely evidence that says those trials are reasonable under good ethical practices, and likely to succeed.

Ideally, you would want to be careful which gene you pick (for instance, not a gene that you can easily overshoot the 'dosage' of), and include some ways to deactivate the gene.