New Therapies for IBD: From the Bench to the Bedside
New Therapies for IBD: From the Bench to the Bedside
Besides targeting specific molecular components of the adaptive and innate immune systems, a final method of addressing the pathological inflammation present in IBD is the use of cell-based therapies to stimulate or replace aberrant immune cells. To this end, several therapies involving stem cells or autologous immune cells are in development for the treatment of IBD. These therapies include remestemcel-L (Prochymal) and multistem, which are mesenchymal/haematopoietic stem cell based; PDA-001, which uses placenta-derived stem cells; and OvaSave, an autologous T-cell therapy. All of these approaches are currently in phase I–III trials in either CD, UC, or both.
The results from previous trials of cell-based therapies in small groups of patients with IBD are promising. For example, the use of autologous non-myeloablative haematopoietic stem cell transplantation in 24 patients with severe CD resulted in remission in all the patients treated. Over a 5-year follow-up the percentage of patients who remained relapse free was 91% after 1 year, 57% after 3 years and 19% at the end of 5 years. Another study using mesenchymal stem cells had more mixed results, with only three out of nine patients showing a clinical response and three patients requiring surgery due to disease worsening. Stem cells have also been used specifically to address the problem of fistulas. In a small trial of 10 patients, intrafistular injections of mesenchymal stem cells resulted in sustained complete closure in seven patients as well as a reduction in CD activity. Similarly, the use of adipose-derived stem cells with fibrin glue in perianal fistulas resulted in healing in 71% of patients compared with only 16% healing in patients treated with fibrin glue alone. Despite the success of cell-based therapies, the complex, time consuming and expensive process needed to harvest, expand and transplant the cells makes it difficult to treat large numbers of patients. It is likely that cell-based therapy will be reserved for specific situations such as fistulas and as a last resort when all other treatment avenues have been tried.
Cell-based Therapies for IBD
Besides targeting specific molecular components of the adaptive and innate immune systems, a final method of addressing the pathological inflammation present in IBD is the use of cell-based therapies to stimulate or replace aberrant immune cells. To this end, several therapies involving stem cells or autologous immune cells are in development for the treatment of IBD. These therapies include remestemcel-L (Prochymal) and multistem, which are mesenchymal/haematopoietic stem cell based; PDA-001, which uses placenta-derived stem cells; and OvaSave, an autologous T-cell therapy. All of these approaches are currently in phase I–III trials in either CD, UC, or both.
The results from previous trials of cell-based therapies in small groups of patients with IBD are promising. For example, the use of autologous non-myeloablative haematopoietic stem cell transplantation in 24 patients with severe CD resulted in remission in all the patients treated. Over a 5-year follow-up the percentage of patients who remained relapse free was 91% after 1 year, 57% after 3 years and 19% at the end of 5 years. Another study using mesenchymal stem cells had more mixed results, with only three out of nine patients showing a clinical response and three patients requiring surgery due to disease worsening. Stem cells have also been used specifically to address the problem of fistulas. In a small trial of 10 patients, intrafistular injections of mesenchymal stem cells resulted in sustained complete closure in seven patients as well as a reduction in CD activity. Similarly, the use of adipose-derived stem cells with fibrin glue in perianal fistulas resulted in healing in 71% of patients compared with only 16% healing in patients treated with fibrin glue alone. Despite the success of cell-based therapies, the complex, time consuming and expensive process needed to harvest, expand and transplant the cells makes it difficult to treat large numbers of patients. It is likely that cell-based therapy will be reserved for specific situations such as fistulas and as a last resort when all other treatment avenues have been tried.