Editorial on In Utero Gene Therapy

The journal Molecular Therapy has an interesting editorial on In Utero Gene Therapy by Charles Coutelle. Here is a sample:

In utero gene therapy in humans remains controversial, despite the increasing use of fetal gene delivery in animals. Advantages of in utero gene therapy include the beneficial vector-to-cell ratio, the presence of expanding and developing stem cell populations during fetal life, the possibility of achieving tolerance against vector and transgenic proteins, and the prospect of preventing irreparable tissue damage associated with early-onset inherited disease. Therapeutic proof of principle by this approach has been demonstrated in several rodent models of human genetic conditions. Recent advances in fetal medicine—particularly in imaging and minimally invasive intervention—have opened the way, in large animal models, for clinically relevant delivery of gene therapy vectors to virtually any fetal organ. However, although postnatal gene therapy has seen its first successful clinical applications, no trials are planned for human gene therapy in utero, now or in the near future. Indeed, many view the concept as having only academic value, with no potential for translation into the clinic.

At present, the options for a couple at risk of having a child with a serious mendelian disease are preimplantation genetic diagnosis and embryo selection, abortion, or caring for an affected child. Safe, effective, and curative gene therapy in utero would be by far a better option. Research toward this goal may also facilitate postnatal gene therapy by providing insights into the problems associated with stem cells and immunologic rejection later in life.

The most frequent objection to in utero therapy is that, if a fetus is shown to be affected by a serious inherited disease, abortion is a logical and clinically safe procedure that should not be rejected in favor of the initially unproven outcome that would result from a gene therapy approach in utero. However, it is not rare for a family to decide against abortion, even though this may mean assuming the burden of caring for an affected child. Prenatal gene therapy may offer an answer to this dilemma, although the first families to choose this option would certainly face a difficult decision because of the perceived and real dangers, and the unproven reliability of the procedure.

....We are only at the beginning of the development of effective therapeutic approaches for severe human genetic diseases. These conditions are so varied and complex that each will require a specific approach by drug, cell, or gene therapy. None of these approaches will provide a "magic bullet," and, until we have clinically proven results, no one can predict which approach will be successful for which disease. In utero gene therapy should thus have a place in our potential arsenal.

Cheers,
Colin