Gene therapy and X-linked SCID: Where are they today?

Yesterdays post got me so annoyed and flabbergasted-- I needed to read a nice MLV paper to cheer me up. And nothing cheers me up like using gene therapy on kids with genetic diseases, allowing them to live pretty much normal lives:

Efficacy of gene therapy for X-linked severe combined immunodeficiency.

Most readers of ERV know this story. Some baby boys are born with a malfunctioning gene, totally screws up their immune system. The babies are fine, for a while, because they get antibodies to most things from their mothers milk. But when its time for baby to start making his own immune system, things go down hill, very fast. Babies with X-linked SCID usually die before the age of two from opportunistic infections.

Bone marrow transplants can help, but not only is it hard to find matches, kids die from this procedure (72% survival rate). So in the late 1990s, French scientists got the idea to cure these kids with gene therapy. Take bone marrow cells from the kid, treat them with a MLV-gene therapy vector containing a functional copy of the gene these kids need. And YAY! Cured kids!

They tried this on nine babies. Babies. About seven months old :-/

And four of them got cancer, because thats kinda what retroviruses do. When you randomly insert into a genome enough times, you are eventually plop into a tumor suppressor, or right upstream of an oncogene.

And one of those kids died.

So this kind of gene therapy was shut down. Immediately. Cant be givin babies cancer.

... But what ever happened to the other eight kids?

The other three kids with cancer got chemo.

They are still alive today.

Seven of the eight surviving kids have (almost) normal immune systems. They are now 8-11 years old, and can live in the outside world, fighting off regular childhood infections like regular kids:

Common γ-chain gene transfer into autologous CD34+ cells led to sustained reconstitution of the T-cell pool and protection from infections, but at the risk of the development of T-cell acute lymphoblastic leukemia. All children except one, including the three survivors of T-cell acute leukemia, could live normally in a nonprotected environment and cope with microorganisms (e.g., VZV) without harmful consequences while growing normally.

... Overall, the present study confirms the expectation that ex vivo gene therapy for SCID-X1 can result in long-term correction of the SCID phenotype.

77.8% of the kids that got this therapy were, functionally 'cured'. One didnt respond well. One died from a complication we now know to look for (88.9% survival, but now we have a red flag to look for. that number is only going to improve).

And, this is, at this point, very old technology. Well over a decade old. Gene therapy vectors and our technology/methodology has improved with time (please tell me you all can access this article- its a very good retrospective):

The transduction technology has now been considerably improved and safer vectors have been designed (as described above), so it makes sense to view gene therapy as an option for the treatment of SCID.

... Just as transplantation of HSCs emerged from the pioneering work in primary immunodeficiency diseases more than 40 years ago, it is possible that the early success of gene therapy for SCID could pave the way for the development of gene-based treatments of other diseases of the hematopoietic system. The field's highs and lows have been artificially amplified by the media and the scientific community. A more cautious, better balanced view should prevail. Immunologists should also consider gene therapy for its 'bystander' effects; that is, the provision of tools for the in vivo study of hematopoiesis-lymphopoiesis in humans.

If Ive said it once, Ive said it a thousand times: "I LOVE THE FUTURE!!!"

More like this

I think I say this every time that an article like this is posted:


By Kemanorel (not verified) on 24 Aug 2010 #permalink

No access unless we pay 18 bucks.

...but we get the intro and I am assuming the copy paste in the O.P. is the conclusion?

By Prometheus (not verified) on 24 Aug 2010 #permalink

The research is still ongoing though. After checking the viral vector it was discovred that the "random" sequences wasn't random but rather had more similarities to (now known) oncogene precursors.

The gene therapy clinical trials are on going in several countries in Europe with collaboratino with some US research groups in big collaborations.

So, there is definetly things to look forward to! :)

(on a side note; yes, it was too bad that most funding turned away real wuick when the one death occurred. Although, now it seems to be more positive approach especially since the vectors have been totally redesigned)

It's a promising end to a story that at one point seemed quite disheartning.

Gene therapy has a bumpy ride over the past 15 years but it is finally showing its worth in the clinic. As well as the SCID treatment there have recently been successful early trials of gene therapy for X-linked adrenoleukodystrophy and Leberâs congenital amaurosis:…

Add to that the promising results obtained with phase I trials of gene therapy to treat HIV infection and clinical trials in the pipeline for Pompe disease…, and the picture starts to look very interesting. The Genetics revolution may be taking a bit longer than everyone initially hoped, but it is happening!