Monday, October 26, 2009

We live in exciting times! Blindness cured!

Well, not exactly, but some sensationalism is warranted.  This is mostly a follow up study that has been ongoing for the past 2 years or so, but researchers from UPenn and the Children's Hospital of Philadelphia have successfully used gene therapy to reverse (for the most part) the visual impairments associated with a disease known as Leber's congenital amaurosis, or LCA.  To be clear, this is not a cure for all types of blindness (that is, blindness due to other causes), nor is it even a full cure for LCA, as none of the patients have regained completely normal vision (though they have made tremendous improvements), and the mutated gene targeted in this study only accounts for 8-16 % of all LCA cases.  Still, this is incredibly promising research, for several reasons.  First, and most obvious, despite not being a complete cure, a single injection of a gene therapy mostly reversed LCA associated blindness to the point where half of the patients are no longer legally blind and can even navigate obstacle courses in low light conditions.  The second major aspect of importance is the gene therapy itself.  In this case, an adeno-viral vector was designed to insert a functioning gene (called RPE65, or retinal pigement epithelium-specific protein that weighs 65 kilo-Daltons) in place of a mutated version that underlies LCA in a small proportion of cases.  What's amazing is not the virus mediated transfection of the gene, as this is a technique that has been around for a while, and used successfully many, many times in mice and other experimental animal models.  What's exciting about the use of this technique in humans is that the FDA is very very cautious when it comes to allowing it to be used on humans.  Mainly, they are concerned because a virus is used to carry the gene and insert it into human cells, and they are also concerned that, in the long term, messing with the DNA in the cells could increase the risk that the infected cells will become cancerous.  Of course, the viruses used in gene therapy have been engineered so that they cannot replicate, and therefore cannot cause disease (much like attenuated viruses that are used in vaccines).  But the worries about cancer can only be alleviated when we have a large enough group of patients who we can follow over time to see whether or not they develop any tumors.  As mentioned, this particular study is already 2 years in the making, and, so far, there does not appear to be any increased incidence of cancer, which is very exciting and promising (though, of course, these patients will still need to be monitored as the years go by).  Finally, the fact that these viral mediated gene therapies have been used and validated so extensively in lab animals is what made this therapy possible (and successful) in humans.  Thus, another major underpinning of this study is how it demonstrates the importance of lab animal use in biomedical research. 
I also liked how the researchers used each patient as their own control by injecting the therapy into only one eye.  In this way, they could compare their results from the treated eye to the untreated eye, and since both eyes are in the same patient, they should be as close to identical as possible including the amount of bloodflow they receive, etc.  In this way, the researchers could be sure that it was really their treatment that made the patient's eyesight better, and not a natural regression of the disease (or a miracle).  They can tell this because if one eye gets better and the other doesn't (assuming it's the treated eye that gets better) then the gene therapy appears to work.  If both eyes stay the same, or get worse at the same rate, then the therapy didn't work.  And, if the treated eye actually gets worse faster than the normal rate of degeneration due to the disease (which should be evident in the untreated eye), they will know that there is something wrong with the treatment.  Of course, this type of design makes it difficult to rule out any placebo effect (since, I'm assuming, the patients all know that at least one eye is going to be receiving the treatment), but given the remarkable results, I think we can rule out the placebo effect, or, if not, apparently, we can use it to reverse certain types of blindness.  Either way, I think we should be happy.

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