Research Advisory Chairperson Addresses Recent Gene Therapy Disappointments

Michael Silver, Chairperson of CFRI's Research Advisory Committee

Fall 1995

In the recent edition of The New England Journal of Medicine (9-27-95), researchers reported discouraging results from two separate gene therapy trials where scientists were attempting to cure disease (cystic fibrosis in one study and Duchenne muscular dystrophy in the other) by adding healthy genes to cells with faulty genes. In the CF study, attempts in the laboratory looked promising. But attempts to use an inactivated cold virus to add healthy genes to cells lining the nose of 12 CF patients failed. Dr. Richard Boucher of the University of North Carolina reported that the installation method did not work. Nasal cells took up so few genes that the gene therapy had no effect, and using more viruses to transfer more genes irritated the patients' noses.

These results, while discouraging at first glance, should not be surprising. Many researchers had surmised that there might be problems with the adeno-virus approach while still anticipating the results of these studies. While a "cure" may be further off than originally hoped, we can still remain optimistic. It is important, however, to also be realistic about the difficulty of our task. There is still much we do not know about how the cell works at a molecular level (which is where the basic CFTR protein defect occurs). Such work is long and arduous but extremely helpful to all other kinds of research (including clinical and gene therapy). It is also important to be aware of how much we do know. We have successfully created a functional gene, one that contains healthy CFTR. The difficulty that remains is the method for getting that gene into the cells that need it. In the above study, the disassembled cold virus approach appeared reasonable because cold viruses are extremely efficient at injecting DNA into the human lung cell. But then the human body is also highly efficient at fighting this mechanism, and therein lies the problem with this type of delivery. Keep in mind that several other approaches are being explored by talented researchers.

We can anticipate more "failures" because it is human nature to leap into the study of new, undeveloped theories in an effort to be the first to discover a treatment that will save lives. Researchers may discover the answer that way, but more probably it will be a long process involving a lot of hard work, including much more basic research into understanding the fundamental defect. We are still moving forward at a very fast pace. And so-called failures yield solid information which pushes us further down this road. In the meantime, I encourage you to keep up your efforts to raise money for sound research studies. Ultimately, it's just a matter of time before gene therapy works!

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