How was gene therapy able to cure diseases through the transformation of actively dividing cells?

Question

I thought that gene therapy, when performed on target cells that regenerate themselves constantly, can be effective for a limited time only. I.e., the effect gradually wears off after a while, depending on how fast the target cells renew themselves. In other words, the patient needs to continue receiving gene therapy every so often to keep getting desired effect. On the other hand, when targeting cells that do not divide/renew, such as an eye, gene therapy can and actually did cure blindness once and for all, and the patient no longer needs gene therapy injections. So what about the other diseases that gene therapy allegedly cured? I think they include blood disorders like hemophilia and some serious immune system disorders? I thought they mainly involved cells that do regenerate, like bone marrow and liver?

Answer 1

In a very general sense, the response to your question is "It depends'"

Gene therapy's effectiveness is disease & cell type specific. A fast growing cancerous cell would be a logical place to target for gene therapy, but they have also, in a few instances, become even more deadly to the patient afterwards (see French Leukemia Gene Therapy fiasco). An eye cell may be at the low end of the number of cell divisions, but if the vector that is used to target the disease state in the eye is driven by a strong, eye specific promoter (and the disease is caused by too little of the protein), then cell division may not be relevant. Again, its cell/disease specific (do i want to target a stem cell population so i can generate a clonal population of cells to cure the disease, or do I simply want to restore gene expression to a relatively normal level to at least make the disease chronic and livable vs. acute and fatal.

Not a perfect answer (or the one you were hoping for), but you may wish to hone your question down to get a more specific answer.

Cheers,

drsjp

Answer 2

Hi, great question! This is indeed one, if not the most significant, of problems with gene therapy. You are absolutely correct: gene therapy isn't able to achieve long-term results for cells that divide very quickly, and this is the main reason (among many, many others such as immune responses) that it isn't used as widely and is for the most part only in phase I testing. It does wear off, and patients usually require multiple treatments.

Here's an interesting article on the hemophilia example that might interest you: http://www.bloodjournal.org/content/131/9/952?sso-checked=true