'Developmental Candidates' for Cell-Based Therapies for Parkinson's Disease (PD)

Evan Snyder
Sanford-Burnham Medical Research Institute
Early Translational: TR1-01267
Status: Active
$3562824.00

The Early Translational Awards, which are funded annually, either lead to a drug candidate for an unmet medical need or address a bottleneck in the development of new therapies. The 16 Early Translational I awards worth $71,570,007 were awarded on 4/29/09. You can learn more about the awards by reading the RFA or reading the press release.

Public Abstract (provided by applicant)

Parkinson's Disease (PD) is a devastating disorder, stealing vitality from vibrant, productive adults & draining our health care dollars.It is also an excellent model for studying other neurodegenerative conditions. We have discovered that human neural stem cells (hNSCs) may exert a significant beneficial impact in the most authentic, representative, & predictive animal model of actual human PD (the adult African/St. Kitts Green Monkeys exposed systemically to the neurotoxin MPTP). Interestingly, we have learned that, while some of the hNSCs differentiate into replacment dopamine (DA) neurons, much of the therapeutic benefit derived from a stem cell action we diseovered a called the

Statement of benefit to California (provided by applicant)

Not only is Parkinson's Disease (PD) a devastating disease in its own right-- impairing typically vibrant productive adults &draining our health care dollars -- but it is also an excellent model for studying other neurodegenerative diseases. We have discovered that stem cells may actually exert a beneficial impact independent of dopamine neuron replacement. As a result of a multiyear study performed by our team, implanting human neural stem cells (hNSCs) into nearly the most authentic, representative, and predictive animal model of actual human PD (adult African/St. Kitts Green Monkeys exposed systemically to the neurotoxin MPTP), we learned that the cells could reverse severe Parkinsonian symptoms by protecting endangered host dopaminergic (DA) neurons, restoring equipoise to the cytoarchitecture, preserving the host nigrostriatal pathway, and reducing alpha-synuclein aggregations (a pathological hallmark of PD). This action, called the "Chaperone Effect" represents a more tractible near-term method of using cells to address an unmet medical need. However, many questions remain in the process of developing these cellular therapeutic candidates. A major question is what is the best (safest & most efficacious way) to generate hNSCs? Directly from the fetal brain? From human embryonic stem cells? From human induced pluripotent cells? Also, would benefits be even greater if, in addition to harnessing the Chaperone Effect, the number of donor-derived DA neurons was also increased? And could choosing the right stem cell type &/or providing the right supportive molecules help achieve this? This study seeks to answer these questions. Importantly, we will continue to use the most representative model of human PD to do so, a model that not only mimics all of the human symptomatology but also all the side-effects of treatment; inattention to this latter aspect plagued earlier clinical trials in PD. Because of the unique team enlisted, these studies can be done at a fraction of the normal cost, allowing for parsimony in the use of research dollars, clearly a benefit to California taxpayers. Not only might California patients benefit in terms of their well-being, and the economy benefit from productive adults re-entering the work force & aging adults remaining in the work force, but it is likely that new intellectual property will emerge that will provide additional financial benefit to California stakeholders, both citizens & companies.