Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous experiments in Aim 1 of our grant have demonstrated that, even though the porcine spinal cord seems to tolerate escalating numbers and volumes of injections, the severity of acute transient morbidity should not be neglected. Moreover, escalating numbers and volumes of injections seem to be associated with lack of accuracy and reflux. Histological analysis will further assess morbidity by determining whether there is a reduction in the number of motor neurons or not in grafted areas in comparison with intact segments. Histological analysis will also determine whether reflux occurs with volume escalation as well as with fast (hand-held) injections. At the same time, little is understood about the appropriate immunosuppressive therapy for spinal cord stem cell transplant recipients. In our ongoing human trial, aggressive immunosuppressant therapy has formed the single biggest source for adverse events. Aim 2 will help us to minimize immunosuppression, preventing needless complications.