SYDNEY, Australia — A molecular biologist working mainly at the University of Auckland's School of Medicine, in New Zealand, is looking at a number of applications for a new technique that strongly suggests genetic therapy is possible through pills.
Matthew During, who worked in the departments of internal medicine and neurosurgery at Yale University until 1995, told BioWorld International he is examining several applications for the technique, the first involving lactose intolerance in cattle.
During said he is working with the New Zealand dairy industry on possible ways to treat lactose intolerance in cows, which is a problem in New Zealand and a major problem in Asia. Beyond that are clinical applications for diseases such as diabetes and hemophilia, he said.
During, who also holds an appointment at the CNS Gene Therapy Center at Jefferson Medical College, in Philadelphia, was head of a team of six scientists in New Zealand and the U.S. that orally administered to rats the engineered combination of an adeno-associated viral vector and a beta-galactosidase gene (to encode for the missing lactose protein).
In a paper published in the October issue of Nature Medicine, the group says the combination managed to cross the surface layer of the gut and implant the gene in the gut cells. Further, in repeated trials, the scientists found that the gene was still actively expressing its protein up to six months after treatment.
The Nature Medicine paper, titled "Peroral gene therapy of lactose intolerance using an adeno-associated virus vector," states, "A gene pill associated with highly efficient and stable gene expression might be a practical and cost-effective strategy for even relatively mild disorders such as lactose deficiency."
The paper notes that lactose intolerance is the world's most common genetic disorder, affecting entire populations in some of Southeast Asia, and is commonly associated with a reduction in intestinal lactase activity.
Although the condition is readily controlled by omitting foods containing lactose from the diet, those omissions, notably a reduction in calcium intake, can have clinical effects.
A commentary on the paper in the same issue of Nature Medicine, written by a team headed by Eric Alton at the Ion Transport Unit at the National Heart and Lung Institute, in London, states that the potential use of gene therapy for treating human diseases has received a "welcome boost" from the During paper.
The commentary also notes that investigators achieved an astonishingly high level of gene transfer across the epithelial (gut surface) barrier, and that "widespread and intense gene expression" occurred within a few hours of oral administration.
A number of problems remain, including the fact that the material was put into the mouths of the rats through a tube rather than in pill form.
However, During is hopeful that the research will lead to genetic therapy through pills. He said his team has worked out all aspects of the mechanism involved in the gene transfer. In addition to the New Zealand dairy authorities, a number of major pharmaceutical companies have shown interest in the work, During said. *