Long-term Administration of Intrathecal Mesenchymal Stem Cells in Multiple System Atrophy – A Compassionate Use Experience (S18.004)

Objective: To explore the long-term safety of repeated intrathecal administration of autologous mesenchymal stem cells (MSCs) as therapeutic approach to multiple system atrophy (MSA). Background: We recently completed a phase I/II dose-escalation study of intrathecally administered autologous, adipose-derived MSCs in MSA. The study showed a favorable safety-profile and treatments were well tolerated up to a dose of 5 × 107 cells per injection. There were compelling clinical and biomarker efficacy signals supporting continued exploration of this approach. Design/Methods: Patients who completed the original phase I/II study were invited to receive additional intrathecal MSC administrations of 5 × 107 cells per injection every 6 months. Exclusion criteria included faster than expected disease progression and an advanced disease stage unlikely to benefit from this compassionate extension. Patients were followed with serial clinical, laboratory, and MRI surveillance. Primary endpoints were frequency and type of adverse events (AEs); secondary endpoints included measures of disease progression (Unified MSA Rating Scale, UMSARS). Results: Of 16 patients invited for this study extension all chose to participate. The protocol is ongoing and patients have received up to 7 additional injections. Repeated injections have shown a similarly favorable AE profile as the original trial. Main AEs continue to be abnormalities on MRI imaging of the cauda equina and self-limited low back discomfort, in none of the patients troublesome enough to decline further treatments. The observed rate of disease progression in the first year of this extension study (UMSARS Total 43.4±12.6 at baseline vs. 48.3±14.2 at 12 months) remained slower than expected, but the efficacy signal seemed weaker as the disease progressed. Conclusions: Repeated, long-term intrathecal MSC administration in MSA is safe and well tolerated. The efficacy signal observed at early disease stages continues to be seen but seems to decline at later disease stages. Disclosure: Dr. Singer has nothing to disclose. Dr. Dietz has nothing to disclose. Dr. Zeller has nothing to disclose. Dr. Gehrking has nothing to disclose. Dr. Schmelzer has nothing to disclose. Dr. Sletten has nothing to disclose. Dr. Gehrking has nothing to disclose. Dr. Coon has nothing to disclose. Dr. Sandroni has nothing to disclose. Dr. Benarroch has nothing to disclose. Dr. Bower has nothing to disclose. Dr. Hassan has nothing to disclose. Dr. McKeon has received research support from Medimmune, Euroimmun, Grifols and Alexion. Dr. Schmeichel has nothing to disclose. Dr. Minota has nothing to disclose. Dr. Low has nothing to disclose.