Gene Editing Offers Hope For Treating Duchenne Muscular Dystrophy (nytimes.com)

schwit1 writes with news that scientists have used a new gene-editing technique called CRISPR to treat mice with defective dystrophin genes. This is the first time that such a method has successfully treated a genetic disease inside a living mammal. The Times reports: "Three research groups, working independently of one another, reported in the journal Science that they had used the Crispr-Cas9 technique to treat mice with a defective dystrophin gene. Each group loaded the DNA-cutting system onto a virus that infected the mice's muscle cells, and excised from the gene a defective stretch of DNA known as an exon. Without the defective exon, the muscle cells made a shortened dystrophin protein that was nonetheless functional, giving all of the mice more strength."

Comments

Quirks and Quarks

[lazarus]

Quirks and Quarks did a podcast very recently about this technology and its application on a particular strain of MD. This work was done (by Dr. Ronald Cohn from the Hospital for Sick Children in Toronto) on living cells however, not live mammals. The podcast does go into a high level and easily understood description of how the technology works. Fascinating stuff.

Hope is good

[rmdingler]

1)Have a little faith. The FDA, a persecuted entity that withholds miracles from the condemned, is at the very least a science-based bureaucracy that attempts to keep untested cures out of the hands of the desperate. FWIW, promising solutions to fateful childhood diseases such as this will be allowed to proceed much sooner than your estimations in medical trials.

2)Remember the religious furor over stem cell research? The same God didn't make it mantra faded quickly when the technology began to pan out. Turns out, a potential cure in the hand for a loved one wins out over some message interpreted from a thousand-year-old-tome.

Re:Hope is good

[Anonymous Coward]

Christians do not have a problem with science or medicine. We have a problem with killing babies and using their body parts. There are now ways to produce stem cells without killing babies and so stem cell research is no longer an issue. The only Christians that have a problem with at least some medical technology (such as blood transfusions) are the Jehovah's Witnesses. They are a small minority Christian denomination.

Re:Hope is good

[fuzzyfuzzyfungus]

So long as it isn't a germline modification there will probably be some enthusiasm for even high risk treatments. DMD reliably cripples and then kills you in a time long enough to be an agonizing ordeal and short enough that you can be said to have died tragically young. When Plan A sucks just that much, even serious side effects start to look pretty good.

If it is a germline modification, or if somebody can't keep their genetic engineering virus from hopping around, a lot more caution will be warranted because removing a change committed to the wild will be a real problem; but this is a nasty disease with a lousy prognosis so if the risks are confined to the patients they will likely be tolerated pretty well.

That's actually what ended up happening to thalidomide. The FDA's refusal to approve a zesty teratogen for marketing to pregnant women was roundly vindicated in hindsight; but it has some niche applications in situations where the risks are lower and the diseases more serious.

Re:Hope is good

[tburkhol]

The practical application of this form of treatment will (as all three papers do) use systemic, viral delivery, meaning all cells will be affected. You can modulate the probability a little by selecting a virus with affinity for particular tissues, but there will still be germline modifications. If you're really worried about that, you make vasectomy a required co-treatment.

It's still a long way from useful. All three papers report similar results: 2-5% changes in the DNA pool; 40-60% changes in the mRNA pool; 20-30% reduction in functional deficits. In a mouse model with a homogeneous genetic defect and without severe pathology

The results are pretty comparable to targeted exon skipping treatments, which started around 15 years ago and have made small human trials without serious adverse results. It's exciting to see research starting to make progress on fixing diseases where the root cause has been known for 40+ years, but the science (nevermind the FDA) is still 10+ years away.

Re:Hope is good

[Anonymous Cow Ward]

Many molecular biologists seem to have this hubris that they completely understand the mechanics of DNA and genes. They are so specialized, they do not know what their tinkering may do to an organism down the road and long after they have been published or even dead.

As a molecular biologist, most of us know that we don't completely understand the mechanics of DNA and genes. We do, however, know a lot more than the average person, and we know a lot about the dystrophin gene, as we've been studying it for a long time. We also know that even if we do screw something up, it's unlikely that it'll cause something worse than DMD already is. Furthermore, this cure - and indeed, any gene therapy cure that could go to clinical trials at the moment - is not passed on in the germ line, meaning it's not heritable.

This technique may for instance cause sever cardiovascular issues. The heart is a muscle and when they get too muscular you get diseases like cardiomyopathy.

Do you really think this is something they haven't considered? Yes, the heart is made of muscle, but cardiomyocytes are different from skeletal myocytes. Furthermore, the gene delivery treatments used to target skeletal muscle are generally different than what you'd use to target the heart, and of course they aren't going to ignore the heart, they aren't idiots. They aren't so focused on "their field" that they'd ignore an organ that's affected by DMD in their analyses.

Let's approach this with caution, NOT phobia...

[jeffb (2.718)]

I know there are concerns around human genetic manipulation, but there are a lot of people suffering in its absence. I'd be willing to take the risk on a therapy like this if I were suffering from a debilitating or fatal genetic illness. Furthermore, I am ready to shoulder my portion of the societal and ethical risks entailed by others testing it.

Re:Effects on progeny?

[Anonymous Cow Ward]

This is true - at the moment, there is no significant research using replicating gene therapy vectors for treating genetic diseases. Anti-cancer gene therapy vectors often are replication-competent, but for treating things like DMD or hemophilia the vectors cannot replicate.

Re:Hope can be horrible

[morethanapapercert]

My son has Duchennes Muscular Dystrophy. He's 10 now and we've been waiting for the exon skipping anti-sense therapy trial you referred to for over a year now. Canadian stage 1 trials were just concluding when we got the diagnosis, we've been told he will only be accepted into the stage 2 trial (when it finally opens) if he is still walking. So now we are in the grim race to keep him ambulatory long enough to qualify for the trial whenever that happens to be. Even the researcher himself cannot give us even a loose estimate of how that will take, since stage 2 trials will only get approved after the stage 1 data has been crunched and reviewed and crunched again by Health Canada.

We were told about the CRISPR/CAS9 approach being tested in animals, but as you note, it is even further down the road then anti-sense therapies. Right now we have to hope that our son can get access to the anti-sense therapies in time and that this will buy him the time he needs for the CRISPER/CAS9 approach to get approved.

The part of it that is eating us up every day is that, even our most optimistic guess for when each therapy will become available isn't soon enough for even our most optimistic prognosis for his condition. The most likely outcome is that he will be in the wheelchair full time and require assistance eating before the anti-sense therapy becomes available and that he will be dead just before the CRISPR/CAS9 "cure" gets full approval.