March 4th, 2004
Boston Cure Project
Autologous hematopoietic stem cell transplantation (HSCT) is a current experimental therapy being tested against aggressive forms of MS. In this procedure, stem cells are harvested from a patient (generally from the blood), most of the remaining immune cells are destroyed via chemotherapy and/or radiation, and the stem cells are then reintroduced so that they can rebuild the immune system. The idea is to destroy any pathogenic immune cells that are driving the disease and then "restart" the immune system. This technique has shown some promise in the few MS trials conducted to date, but the mechanisms through which its clinical benefits have been achieved are unknown.
To help explore the immune system events that occur after HSCT in MS, a small study (4 people) was conducted to analyze T cell characteristics in stem cell recipients. The scientists conducting the study collected and analyzed blood samples from each subject before treatment, in the month after treatment, and then at the 3, 6, 9 and 12 month points. They found that the T cell population was restored in two phases, the first cell expansion being driven by T cells surviving the immune ablation, and the second driven by maturation of the transplanted stem cells. They also found that the properties and composition of the population of the reconstituted cells were similar to the original population before the HSCT treatment. The authors did not find this surprising since the stem cells were introduced into the same environment from which they came. However, they noted that at some point this could lead to redevelopment of aberrant immune function and that autologous HSCT should be compared with transplantation of cells from healthy donors.
The type of work presented by this study is important for a couple of reasons. First, because there are so few options for people with rapidly progressing MS, HSCT is likely to receive more attention in the future as it seems to be able to halt progression (at least for a time). Therefore, understanding how it works will help researchers further develop the therapy to deliver optimal benefits. Second, knowing whether and how HSCT works will provide valuable information about MS causes and disease mechanisms. If MS truly is driven by autoreactive T and B cells, then presumably completely replacing them with non-autoreactive cells will stop the disease. Further investigations into the course of events following HSCT should therefore prove extremely helpful in understanding the disease itself.
Copyright © 2004, Boston Cure Project