Using explicit criteria and a stringent scientific review process, The Bachmann-Strauss Dystonia & Parkinson Foundation encourages research designed to transform the care and treatment of dystonia and Parkinson’s disease. For 2012, a one-time special Request For Proposal (RFP) focusing on dystonia research was released by the Foundation. Following intense review, the Foundation’s Scientific Advisory Board awarded two interrelated grants. The first grant was awarded to H.A. Jinnah, MD, PhD, Professor, neurology, human genetics and pediatrics, Emory University, and the second to Cristopher Bragg, PhD, Assistant Professor of Neurology, Massachusetts General Hospital. The Board believes these gifted researchers have the potential to develop bold new directions in dystonia treatment.
The goal of Dr. Jinnah’s project – the Dystonia Coalition iPS Resource - is to develop a resource for the collection of skin samples for making fibroblast cultures for dystonia, to create stem cells from these fibroblasts to share with dystonia investigators, and to begin to examine the defects in these cells after they are converted into dopamine neurons.
Using newly developed technology to study neurons of different motor pathways, Dr. Jinnah explained that this technology involves taking a small skin sample from patients with dystonia, growing living fibroblasts from the skin, and then converting the fibroblasts into stem cells for making neurons. These stem cells can be used to generate a variety of different types of neurons. Thus, it becomes possible to have an unlimited quantity of different types of neurons for many different types of studies. As these cells are made from skins samples of dystonia patients, they will contain the genetic defects responsible for the disorder.
Dr. Bragg’s project - Generating Isogenic Dystonia iPS Cell lines with Custom TALE Nucleases - will generate iPSCs to different genetic causes of dystonia by turning normal cells into cells with dystonia mutations with TALE nucleases. Essentially they will be able to create iPSCs to any genetic form of dystonia using TALE technology. Dr. Bragg will also collaborate with the Jinnah laboratory in developing and comparing the different dystonia iPSC models. Directly comparing TALE nuclease -generated iPSC lines to ones generated by reprogramming patient fibroblasts can provide a lot of useful information.
The funds provided by The Bachmann-Strauss Foundation will support efforts to derive iPSCs by different methods. The work will take place over the next two years and will proceed in parallel with Dr. Jinnah’s lab. Dr. Bragg, explained, “Once our labs have derived iPSC models, it will be highly useful for us to coordinate functional analyses of the different models within the same assays, i.e., Dr. Jinnah’s group could potentially differentiate all lines in the same platform and characterize morphologic features, while our group could perform transcriptional profiling on all lines.”
In seeking proposals from extraordinary researchers like Drs. Jinnah and Bragg with the potential for innovative approaches in previously unexplored areas, the Scientific Advisory Board looks for projects that will lead to new tools or new directions for future treatments in dystonia and Parkinson’s disease.