[P3.172] FDA-Approved Phase I Clinical Trial of Autologous Neural Progenitors Injected Intrathecally in Multiple Sclerosis
Violaine Harris, Daniel Koffler, Sydney Chirls, Saud Sadiq
New York, NY, USA
OBJECTIVE: To establish safety and tolerability of intrathecal autologous mesenchymal stem cell-derived neural progenitor (MSC-NP)-based regenerative therapy in MS.
BACKGROUND: There is a critical unmet need to develop therapies that target CNS repair and neuroprotection in order to better help patients with progressive MS. MSC-NPs represent a neural subpopulation of bone marrow-derived MSCs with reduced pluripotency and minimized risk of ectopic differentiation. In preclinical studies in mouse experimental autoimmune encephalomyelitis (EAE), we established that intrathecal delivery of MSC-NPs was associated with cell migration to lesion areas, suppression of local inflammatory immune response, and trophic support for damaged cells at the lesion site. These pathological features were associated with improvement in clinical scores of EAE. Preliminary clinical experience with autologous MSC-NPs in a small number of patients further supports the safety and tolerability of this treatment, and warrants a clinical study.
DESIGN/METHODS: The study is a 20 patient, open-label, phase I clinical study of autologous MSC-NPs administered intrathecally in three injections of up to 10 million cells per injection, spaced three months apart. Pre-administration quality testing of autologous MSC-NPs expanded from bone marrow aspirates includes analysis of sterility, purity, identity, and chromosomal stability. Primary safety outcomes include adverse event assessments. Secondary outcomes to observe trends in efficacy include neurological exam, MRI, evoked potentials, and urodynamic testing.
RESULTS: The FDA-approved study enrolled 20 MS patients with established disability (EDSS 3.0 or greater) and relatively stable disease as evidenced by less than 1.0 point change in EDSS in the last year, and stable MRI disease burden with no gadolinium-enhancing lesions in the last six months. Participant demographics and preliminary safety outcomes will be presented. It is anticipated that data from the first 5 patients enrolled will be presented.
CONCLUSIONS: The MSC-NP trial is the first of its kind to test intrathecal administration of neural progenitors as a regenerative therapy for MS and its results will determine the design of future trials.
Category - MS and CNS Inflammatory Disease: Clinical Science
Tuesday, April 29, 2014 3:00 PM
P3: Poster Session III: MS and CNS Inflammatory Disease: Clinical Trials Outcomes (3:00 PM-6:30 PM)