13 October 2011
In pioneering work published today, researchers have combined gene therapy with stem cell therapy to correct a genetic liver defect.
Writing in Nature, the research team reports work to combat the genetic disorder alpha-1 antitrypsin deficiency (A1ATD), which is caused by a mutation in the A1AT gene and leads to liver cirrhosis. The condition is relatively common, affecting around 1 person in 2000 in Europe, and in severe cases, the only treatment is a liver transplant.
The researchers took skin cells from A1ATD patients and turned them into induced pluripotent stem (iPS) cells. They then used a zinc-finger nuclease molecule (see previous news) to cut out the mutated part of the A1AT gene and replaced it with a normal sequence. Finally, the iPS cells with the genetic correction were induced to form cells closely resembling normal liver cells, and transplanted into mice. Within a fortnight, some of these new cells has become incorporated into the livers of the mice, appeared to function as normal liver cells, and were producing normal human A1AT proteins.
Comment: Although this research has gone only halfway to actual gene therapy in humans – since they have yet to move to clinical trials showing a therapeutic effect in people – it is a very exciting combination of leading scientific techniques that could ultimately create a treatment breakthrough for A1ATD patients.