Will gene therapy eventually cure most ailments?

Maybe ‘ailments’ isn’t the right word…

What I mean is, what are the theoretical limits of gene therapy’s effectiveness? Can we expect to see increasingly effective gene therapies for just about anything negative that we can find a genetic cause for? If, say, we were able to isolate genes that cause male pattern baldness, could gene therapy potentially halt that process? Or if a genetic component of obesity was mapped out, how likely would it be that an effective gene therapy could be applied to help ‘cure’ the condition? What about the potential for developing and using gene therapy to strengthen the human immune system or other ‘enhancements’? Is any of that kind of thing really possible, or is it all the stuff of sci-fi still?

Has it cured ANY yet?

According to these articles from MSNBC, yes:

http://partners.search.msn.com/partner.asp?q=gene+therapy&tballssMSNBC=Go&FORM=MSNBC&RS=CHECKED&dom=www.msnbc.com&un=doc&cfg=MSNBC&v=1&co=50&ba=0

Nope. With only ~35,000 genes, there aren’t enough of them to uniquely specify all the things that can go wrong. There’ll be some important successes, but many ailments with a genetic component will remain hidden behind incompletely understood multi-gene clusters, environmentally induced differential expression, and post translational modification of the coded proteins.

Gene therapy is really a broad range of treatment that all intend to “reprogram” the genome. It has never worked as advertised to date, but there are signs that we are getting edging closer.

The idea is that if gene X is broken, you just cut out the old gene X and splice in the new gene X to every cell in the body. This is far, far, far simpler said than done and nobody has gotten within the same galaxy of this to date.

If it were possible to do the above, there is little potential problems with gene therapy. Any potential problem could be easily repaired, as probably 99% of everything has genetic contribution. About the only thing that doesn’t have genetic contribution is trauma, and even that probably has some genetic contribution, both to preponderance, injury extent, and recovery.

There are a number of hurdles to get over once you have even that solved. Let’s say you have cystic fibrosis because you lack a particular protein called CFTR. You introduce CFTR by gene therapy – now you don’t have cystic fibrosis. But, your body may develop an immune response against the perfect, new, CFTR protein because it does not recognize it as part of your body. After all, it is a new protein to your immune system, just like bacteria and viruses. But by the time we have gene therapy working, I can’t see this problem giving us too much problem.

As to actually finding out the genetic preponderances, yeah that’s gonna be a challenge as Squink pointed out. But, there is going to be a lot of headway into this – haplotype surveys, widescale genotyping. Perhaps in 10 years, it will cost $1000 to sequence a genome. At least if you believe Craig Venter. The more data, the more we can figure out. Also, model systems are quite powerful and we may be able to take some of these things apart in mice or flies before worrying about humans. Transcriptional and to an extent translational control are all under mostly genetic control. We could worry about epigenetics, but if we have all of these genetic problems figured out, we probably will have ways of manipulating epigenetics as well. There are enough people working on it…

In terms of ANY cures, it again depends what you mean by “gene therapy.” The standard gutted adenovirus or adeno-associated virus carrying a new gene which homologously replaces the old gene – that is still years in the future. But simpler strategies have yielded therapies although these are not constant. There are some which are very promising in clinical trials – SCID (severe combined immunodeficiency aka the disease which the Boy in the Bubble had) is a potential that comes to mind. SCID shows definite potential – autologous bone marrow transplant with ex vivo gene transfer is a very viable option. Juvenille type I diabetes is coming up on the horizon for a similar reason. Many diseases are perhaps treatable by giving some bone marrow or other stem cells IV, with ex vivo gene transfer – lysosomal storage disorders, immunodeficiencies, blood dyscrasias, and clotting disorders come to mind.

Perhaps we will start to see crude gene therapy for more diseases in the next few years. Don’t wait up for the inhaler full of CF-be-gone virus available in your corner drug store.

There are hundreds of bumps in the road however. A teenager, Jesse Gelsinger, died in a gene therapy trial in 2000, causing wide spread repercussions about clinical trials and safe administration of high doses of a viral vector. Last year, a child in France developed an apparently gene-therapy induced leukemia.

I wouldn’t hold your breath. Therapies which eventually correct genetic mistakes are bound to happen sometime – there is just so much potential waiting there.