Getting the Green Light

Has gene therapy's day arrived?


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When the pediatrician diagnosed both of my two sons with color deficiency, I learned that they see the world a little differently than I do. They see colors, but they have difficulty differentiating between particular shades of reds and greens or blues and yellows. I’m not even sure which. If they had total color deficiency — color blindness — I would have worried, but as it was, we laughed about their little vision condition. It did not seem like any big loss that their career options might be slightly limited, given the wide realm of possibilities.

So when I first read the news last week that scientists had cured spider monkeys of red-green color deficiency, I thought it was a pretty minor stuff. Big deal, so monkeys can now see more colors than my kids! But then I saw that the advance had come with the use of gene therapy, the long elusive, much hyped, and sometimes maligned approach to fixing genetic abnormalities.

Had gene therapy arrived at last, I wondered. The process is the approach in which scientists attempt to replace defective genes with normal ones, delivered using harmless viruses. The concept became popular in the 1980s along with remarkable advances in the understanding of how specific genes — the working subunits of DNA — play a role in inherited diseases.

The scientific community and the public alike placed high expectations on gene therapy’s potential to cure these genetic abnormalities. For a while, it seemed like the world had found its cure for cancer and Alzheimer’s and so many more human curses. But practical success was extremely limited. Then, when a gene therapy experiment led to the death of an 18-year-old in 1999, it appeared that the approach might be a dangerous misdirection.

Luckily, most researchers were undeterred, although by all accounts they proceeded with more caution. Occasionally over the past decade scientists have published little glimpses that indicate the approach still held promise. Gene therapy for vision disorders, most of which have a genetic component involving the retina, offered a particularly promising avenue. The immune system, which can reject the virus carrying the genes, isn’t as active in the eye. Also, it is possible to measure whether the therapy works with simple vision tests.

And this area is now where the first real successes are occurring. The spider monkey work culminated eight years of research at University of Washington and involved the addition of a missing visual pigment gene, using a human gene because the monkey visual system is similar to that of humans (turns out monkeys can take color vision tests like humans, too). The results proved that the nervous system is capable of responding to newly-added sensory input, at least in the case of color vision.

The work followed other recent advances that use gene therapy to treat a blinding disorder called Leber’s congenital amaurosis (LCA), a rare progressive disease that causes cell death and retinal degeneration. Following successful experiments in dogs, initial safety studies in humans that involve the administration of a therapeutic gene to patients with advanced LCA disease indicate that the treatment is safe and at least somewhat effective. The effectiveness of the therapy remains unknown until younger patients with healthier retinas are treated.

These vision trials are notable for more than just their specific therapeutic utility, or even suggested potential to use gene therapy for other vision diseases, such as age-related macular degeneration. They just might be ushering in a entirely new era for gene therapy by providing hope to the hundreds and hundreds of scientists throughout the world who still pursue this avenue of research. Gene therapy still hasn’t cured the problem of, say, cancer or Alzheimer’s, but it is looking a little more likely that the process really is part of the solution.

Meanwhile, I am left wondering whether I would recommend vision gene therapy to my children, since it seems possible that one day in the not-too-distant future, a simple, safe treatment may became available. I doubt that I would, given the limited upside and the general safety concerns associated with any medical intervention. But who knows, there may come a time for reconsideration. One of these boys could grow up to be a natural born pilot or interior decorator or electrician, except for that pesky color vision problem. By then, gene therapy may have finally grown up, too. • 14 October 2009

SOURCES: Gene therapy for red-green colour blindness in adult primates. Mancuso K, Hauswirth WW, Li Q, et al. Nature. 2009 Sep 16. [Epub ahead of print] [PMID: 19759534]; Safety and efficacy of gene transfer for Leber’s congenital amaurosis. Maguire AM, Simonelli F, Pierce EA, et al. N Engl J Med. 2008 May 22;358(21):2240-8, [PMID: 18441370]; Effect of gene therapy on visual function in Leber’s congenital amaurosis. Bainbridge JW, Smith AJ, Barker SS, et al. N Engl J Med. 2008 May 22;358(21):2231-9, [PMID: 18441371]