Tools of the Trade

I like to think of myself as a manly sort of man. Beyond belching and scratching myself in public, this also means that I can put up drywall, fix plumbing and lay tile (for example). To me, using tools and fixing stuff is part of being a man. So is carrying a Leatherman.

The Leatherman is a folding pocket tool with pliers, blades, screwdrivers and pretty much every basic tool you could need in a hurry. It’s like a Swiss Army Knife on steroids. I love that thing, and I carry it everywhere – even when I’m part of the honour party at a wedding. I get excited when I get to use it, just like when a new Canadian Tire flyer comes to my door.

I also love when new tools are invented in biology, and watching tools that I use develop into potentially lifesaving treatments. A couple months ago I talked about using lentiviral vectors in some of the more mad scientist-type experiments that I do. This tool is based on the HIV virus that gives rise to AIDS in humans, and allows us to put any gene we want into any cell.

For years now, scientists have been saying that this opens the door to what we call “gene therapy,” the treatment of diseases at the genetic level. There are serious obstacles in the way of this approach, however. It remains very difficult to deliver these genes to specific areas, and there are certain safety concerns about inserting pieces of foreign DNA into our own cells – some of our important bits of DNA might be changed and this could have some seriously averse consequences for the patient.

Recently, scientists have managed to use lentiviral vectors to help cure a serious genetic defect in two young boys. The boys have a disease called adrenoleukodystropy (ALD), in which a gene that produces a vital component of our neurons (ABCD1, necessary for myelin maintenance) is mutated and doesn’t do what it should. The disease is always fatal, and is currently treated with very limited success by giving bone marrow transplants from an appropriate donor if one can be found. Sadly, even with this treatment, most children diagnosed with ALD die within 3 years.

The scientists in this case took stem cells from the boys’ own bone marrow and infected them with a lentivirus containing a working version of the ABCD1 gene. They let the infected cells multiply and then put them back into the boys, eliminating a serious obstacle for transplants – the risk of rejection. After 3 years, about 15% of the boys’ bone marrow cells are producing the protein properly and the symptoms of ALD – degeneration of the myelin around neurons – have stopped progressing. The boys are in school and living normal lives.

This is a wild success story for gene therapy, and gives us all reason to be optimistic for future treatments. However, any excitement we have about gene therapies should be tempered. Similar approaches have been used in the past and had disastrous results. In 1999, 18-year-old Jesse Gelsinger died as a result of the injection of an adenoviral vector meant to treat another genetic disease. In 2003, gene therapy for a genetic immune disorder led to the development of leukemia in 2 young patients. However, we seem to be getting better. Gene therapy has been used in one recent clinical trial for treatment of AIDS, and another recent study “cured” colour blindness in monkeys using a similar approach.

Gene therapy is an amazing tool for specific genetic disorders like ALD or Huntingdon’s disease. However, for most neurological and psychiatric disorders, the causes are much more complex than a mutation to a single gene. Lentiviral vectors are not much like a Leatherman – they’re more like a hammer. There are specific jobs where these tools are the best thing going, and others where you might as well be using a saw to screw a shelf onto your wall.

Gene therapy has come a long way in the last 2 decades, but not far enough for my mother, whom I think would like me to start working on a lentiviral vector targeting parts of the Y chromosome to stop myself from engaging in some of the more distasteful of my “manly” behaviours…

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Posted in General science, Molecular biology.

Posted on 09 Nov 2009

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