Stem Cell Injections Prevent Loss of Cerebellar Purkinje Neurons

The most consistent pathological abnormality found in autopsied cases of individuals with Autism Spectrum Disorder (ASD) is a decrease in number of cerebellar Purkinje neurons. Purkinje neurons are at risk in many neurological disorders, and undergo cell death in circumstances that may cause debilitating damage in other brain areas. The investigators’ belief that stem cells may help ASD patients comes from their experiments on mice with different neurogenetic disorders which cause selective destruction of Purkinje neurons. They injected neural stem cells (NSCs) into mouse cerebellum and found that mice injected with NSCs as babies, before Purkinje neurons were destined to die, grew up healthy, with cerebella that contained abundant Purkinje neurons. They established that stem cells had rescued the mouse’s Purkinje cells from dying! Before testing stem cell therapy in humans with brain disorders, the investigators must learn in mouse experiments what types of stem cells to use, how many cells to inject, how often, and by what routes, to maximize their distribution though affected brain regions with minimal discomfort. They have discovered that tissue plasminogen activator (tPA) is increased 10-fold in the cerebellum of one of their mouse mutants, and that tPA reverts to normal in mice they treated with NSCs. Through this project, they tested the idea that tPA may act as a common “death mechanism” in many diseases affecting Purkinje neurons, and that therapy with stem cells should be directed at correcting the chemistry involved in this mechanism. The use of stem cells for rescue of Purkinje neurons would be of benefit regarding restoration of cerebellar function and may provide clues to chemical abnormalities that would lead to therapeutic recovery in brain regions that are more subtly affected in ASD, though with serious behavioral consequences.