The previous blog post pointed out how defects in two genes, Fas and FasL are implicated in a number of diseases and may cause such diseases or increase susceptibility to them. It left open the question of what can be done for people with such defective genes and suffering from associated diseases. I speculate that the treatment process will turn out to be something like this:
1. As a first step, a few drops of blood or a tiny piece of skin would be taken from a person suffering from a disease known to be associated with certain defective genes that have been detected in the patient. For example the defective genes could include Fas and FasL in the case Lupus or Lymphoma .
2. The cells in the blood or skin would be reverted to being induced pluripotent stem cells, known as iPSCs. Technolgy to do this is now being perfected. See the post Rebooting cells and longevity and several subsequent posts related to iPSCs in this blog.
3. Using laboratory techniques of gene splicing, sometimes called DNA editing, the defective Fas, FasL and/or possibly other defective genes will be stripped out of the chromosomes in these cells, and good versions of the same genes pasted in their place. This is accomplished by established techniques of genetic engineering. The results will be the patient’s own pluripotent stem cells with good genes in place of the defective ones. Call these corrected induced pluripotent stem cells ciPSCs.
4. The ciPSCs will be encouraged to reproduce in the laboratory to increase their numbers. This is something commonly done.
5. The ciPSCs will be introduced back into the patient under conditions that they will differentiate into the stem cell types and somatic cell types involved in the disease process. Discovering exactly how to do this is probably the major challenge involved in the whole process. Success has already been realized in getting embryonic stem cells which are like iPSCs to differentiate into certain cell tyles. See the July blog post Embryonic Stem cell research news. Also, we know no immune reaction can be expected because the ciPSCs are the patient’s own cells.
6. As the ciPSCs reproduce and differentiate in the body, they will produce adult stem cells and differentiated tissue cells that are free of the genetic defect. The genetically corrected cells will supplement and possibly in time replace the genetically defective ones. In principle at least, as fewer and fewer body cells possess the genetic defect and more and more are normal, susceptibility to the disease should decrease, the hope being that the disease will go away. The process can be compared to replacing defective car parts with rebuilt ones from the original manufacturer.
Why such a complicated process using corrected induced pluripotent stem cells? If the disease is in T-lymphocytes for example , why not just collect some T-lymphocytes from the patient, correct the genetic defects in them, reproduce them and introduce them back into the body? I think a major problem would be that the body’s hematopoietic stem cells that make new T-lymphocytes would continue to have the genetic defect in them and would continue differentiating and producing new defective t lymphocytes. So, I believe it will be necessary to go to the stem-cell level to have a lasting fix. Many genetic engineering experiments have been tried with ordinary cells but with only poor or mixed success.
If the kind of treatment process I outlined can be realized and fine-tuned, it could possibly be used to control or vanish most diseases related to genetic defects, not just defects in Fas or FasL. I don’t think it will be very long before we start seeing positive results using this kind of process in laboratory animals.