Development of an Adult Adherent Allogeneic Stem Cell Product for Treatment of Parkinson's Disease

Objective/Rationale:
Previously published data illustrates that MultiStem®, an adult stem cell product approved by the FDA for Phase I studies in humans, works through multiple mechanisms of benefit, including immune modulation and neuroprotection, in pre-clinical models of central nervous system (CNS) injury and disease. Translationally relevant experiments are proposed in a pre-clinical model of PD, thereby enhancing the working knowledge of MultiStem, and accelerating the potential clinical application of this cellular product for patients who suffer from PD.

Project Description:
Experiments to be performed include: determining the optimal effective dose of MultiStem and the window of optimal therapeutic benefit (acute vs. chronic) in a pre-clinical model of 6-hydroxydopamine induced PD. Outcome measures to be assessed include: preservation of tyrosine hydroxylase positive neurons by stereology, striatal terminal density, improvements in rotational asymmetry and spontaneous forelimb use in the cylinder test. Brain, blood, spleen and lung tissue will be harvested and analyzed by microarray to assess the effect of MultiStem on neuroinflammation and systemic immune modulation. Data generated from this proposal will be used as part of a pre-clinical data package submitted to the FDA for use of MultiStem for treatment of patients suffering from PD in a Phase I clinical study.

Relevance to Treatment of Parkinson’s Disease:
Until recently, the focus of researchers testing cellular therapeutics for treating PD has been on intracranial implantation in an effort to replace neurons lost due to the progression of the disease. Recently, adult stem cells have shown promise in pre-clinical models by preventing PD associated neuronal death. It is believed that the intravenous administration of MultiStem will provide an improved therapeutic route of administration for this emerging therapy, and will protect dopaminergic neurons by decreasing neuroinflammation.

Anticipated Outcome:
MultiStem administration provides documented therapeutic benefit in multiple models of CNS disease and injury, including stroke, spinal cord injury and traumatic brain injury. Work performed as part of this grant award will demonstrate that intravenous administration of MultiStem provides neuroprotection of at risk dopaminergic neurons in a pre-clinical model of PD. Additional experiments will determine the effective therapeutic dose of cells, as well as the therapeutic window for administering these cells following disease onset (acute vs. chronic).