Friday, July 20, 2012

Will we see gene therapy for eczema?

The European Commission is close to approving the first gene therapy in the Western world, according to the New York Times.

The treatment, called Glybera and developed by the Dutch company uniQure, treats a rare condition in which people are unable to break down fat-carrying molecules.

Gene therapy is one way that I imagine patients of the future might be cured of eczema. Glybera gives us a peek into how that might happen.

In gene therapy, doctors replace a patient’s faulty gene with a good one. The large protein filaggrin is currently the best candidate for eczema gene therapy. Several studies have linked filaggrin mutations to a higher risk of developing eczema.

Filaggrin gene therapy would have to be applied early in life. This is because in our current understanding, eczema is caused by a skin barrier defect that allows allergies to develop after a critical time window. Filaggrin mutations cause a faulty skin barrier. So you’d have to fix filaggrin early, because waiting too long would allow allergies to develop, after which fixing filaggrin solves only half the problem.

Glybera is a biotherapeutic, a gene (length of DNA) that is attached to a well-characterized and benign virus. Doctors will inject Glybera into leg muscles, where the virus infects cells and incorporates itself and the therapeutic gene into the patient's DNA—but only in leg muscle cells, presumably because Glybera gets absorbed locally. Then the patients will be able to break down the fat-carrying molecules, and their blood will no longer be overloaded with fat.

A biotherapeutic for eczema would likely be an intact filaggrin gene incorporated into a similar virus.

Gene therapy for the skin would have to be restricted to skin cells. You could accomplish this with a topical cream or ointment applied in the clinic. I'm guessing you would want to treat your whole skin, not just spots that were flaring up at the time.

How long will it last? The effects of Glybera apparently last for years, probably because muscle cells live a long time. Skin cells are a different matter—they are turning over continually. This could turn out to make gene therapy for skin conditions near-impossible.

But perhaps you could take regular doses—pills or injections—of a gene therapy that includes a genetic switch that turns on only in skin cells.

The critical early window for developing allergies in eczema patients could turn out to be a bonus in disguise. Maybe filaggrin gene therapy would only be required during a window of a few years, after which it could be discontinued and allergies would never develop.

Obviously extensive clinical trials for safety would be necessary. I could imagine this type of therapy becoming available within two decades. My grandchildren could be among the first to benefit.

5 comments:

  1. Hi. Have you read dr Martin rapaports papers on steroid-induced eczema?
    Basically, he is saying that overuse of steroid creams in eczema patients can cause a form of dermatitis known as red skin syndrome and that many people who think they have eczema actually have steroid-induced dermatitis. A japanese dr called dr mototsugu fukaya also has written extensively on the subject, including amazing healing photos on his site. Both papers can be accessed via itsan.org if you care to take a look. I would be interested in your opinion.

    I stopped using steroids back in November and am almost healed. I believe I grew out of my childhood eczema long ago, but my dermatitis persisted because I was using increasingly strong steroid creams.

    ReplyDelete
  2. Thanks for the info, Louise. Glad to hear your own eczema is mostly cleared up.

    I have recently seen press releases from ITSAN. I'll look into it a bit more. I do know that excessive and continued use of strong steroids can thin the skin and reduce the anti-inflammatory effect of the ointment. It seems plausible that in rare cases steroids could somehow irritate the skin themselves (because of steroids or other components). I have trouble believing that something like steroid-induced eczema would be widespread, though. It's not going to be the mystery single cause everyone would like to find. But as I said I'll look into it.

    ReplyDelete
  3. Hi
    Very very intersting article - me and my son have eczema and what a god send to see a cure for him and his kids (when he grows up).
    My son also has a rare metabolic life threating condition and gene therapy will be his way out of that one too - our specialist does confirm she believes a cure through gene therapy will be available to him in his life time.
    So your article/cmments gave me renewd hope.
    I hope for all our sakes a true cure is soon - people don't realise the true evil of eczema.
    Best of luck, Jas (Australia)

    ReplyDelete
  4. I have struggled with hand/foot eczema for about 10 years, but always had dry skin and minor outbreaks even in childhood (I'm now 63). The problem is now worse than ever, perhaps because of the heat here in Arizona. I am especially interested to learn if anyone is beginning to develop a link between the filaggrin gene defect (with its loss of moisture through the skin) and diseases like kidney stones. I have always been a water drinker, but underwent surgery for kidney stones recently--"stay well hydrated" is the mantra, but I wonder if I have a handicap due to the filaggrin gene thing? Thoughts anyone? azluthier@cox dot net.

    ReplyDelete
  5. Wait, wouldn't the new gene-treated skin cells divide to create new skin cells? Just because the gene treated cells die doesn't mean that the effect will disappear, as those treated cells would multiply and produce new cells.

    ReplyDelete