Stem cells: from animal models to clinical practice

Abstract

Despite significant advances in the therapeutics of neurological disease there remain a number of conditions where the possibilities for modification of the natural disease course remain limited. These are commonly disorders with a dominant neurodegenerative component and include major diseases such as Parkinson’s, Huntington’s, amyotrophic lateral sclerosis (ALS) and progressive multiple sclerosis (MS), as well as a multitude of rarer conditions. Stem cell treatments may offer some promise in these conditions, particularly in slowing or reversal of neural degeneration, and have understandably captured the public imagination with their obvious possibilities. Despite a number of early setbacks, false dawns and restricted funding, it now seems that we are entering an era where clinical trials in this discipline are becoming more mainstream and increasingly relevant to practising neurologists. As a result the high expectations of desperate patients may have a chance of being partially realised, and it is likely that a working knowledge of this subject by all neurologists will be of value to enable effective communication with patients. The stem cells employed in trials to date have been of either embryonic or adult human origin. Clearly the principal advantages of embryonic stem cells are that they are pluripotent, highly proliferative in vivo (and therefore a renewable cell source) and have the potential to differentiate into a wide range of adult cells. However, they may still require a degree of immunosuppression for graft survival and their pluripotential nature also means that controlling differentiation remains a significant challenge. In contrast, adult stem cells offer the possibility of autologous transplantation avoiding the need for immunosuppression, but have a more limited differentiation potential. These limitations raise particular issues in trials of neurological disease where access to transplant targets and the sites of pathology are so problematic. In this month’s Journal Club we review three articles on the use of stem cells to treat neurological disease. In the first of these we examine some interesting pre-clinical studies on animal models of Parkinson’s disease, and a new method of generating dopaminergic neurons from stem cells that may be an improvement on more traditional methods. In the second paper we discuss an early phase I trial of fetal derived stem cells for ALS in 12 patients that demonstrates in broad terms the safety of the procedure but also illustrates some problems associated with the required immunosuppression. Finally, we look at a phase IIa trial of adult stem cells in progressive MS, which offers some early promise of altering disease course. These studies also highlight fundamental differences in approach to specific diseases so that in Parkinson’s disease transplanted cells are aimed at accurate differentiation to achieve circuit reconstruction, whereas mesenchymal stem cells aim at providing trophic support.