Dysautonomia Foundation, Inc.

Dysautonomia Foundation Research --
Current Projects 

Ron Goldstein

Generation of human sensory neurons from embryonic stem cells for gene therapy/drug testing and cell transplant therapy for Familial Dysautonomia 

Human embryonic stem (ES) cells were first isolated about five years ago. These amazing cells can be grown virtually indefinitely in tissue culture and have the potential to form any cell type in the human body. These characteristics give the cells the potential to provide unlimited numbers of normal human cells for drug development and, combined with new molecular biology techniques, investigation of the molecular mechanisms of genetic disease.

In addition, if current regulations prohibiting therapeutic cloning are changed, human ES cells could be produced with the genes of the patient, eliminating problems of immunological rejection. Recent work with mouse embryonic stem cells has demonstrated that genetic disease can be cured with a combination of gene therapy of ES and their subsequent conversion to the desired type of cell.

The basic aim of this project is to generate sensory neurons from human ES for drug development/gene therapy testing for dorsal root ganglion (sensory) neurons lost in Familial Dysautonomia. These techniques when developed, should be easily modifiable to produce sympathetic (autonomic) neurons as well. Although there are many laboratories directing the differentiation of human ES to neurons, our project is unique since no studies to date have addressed the production of peripheral (sensory/autonomic) as opposed to central neurons (ie. motorneurons for ALS and dopamine neurons for Parkinsons disease).

In addition to the more controlled and commonly used experimental system of tissue culture, the living avian embryo has been used as “petri dish” for the study of the development of mammalian cells. The experimental accessibility of the chick embryo allows surgical access to sites in the embryo that direct sensory neuron differentiation. We have recently utilized this classic system for studying differentiation of human ES. Importantly for FD research, we found that some of the human cells integrated into the host chick dorsal root ganglion and made cells with the morphological characteristics of neurons. In addition, ganglion-like aggregates of human cells that made proteins characteristic of human neurons were found in the grafts.

Ron Goldstein is associate professor in the Faculty of Life Sciences at Bar-Ilan University in Israel . Ron obtained his PhD from the Center for Neurobiology and Behavior at the Columbia College of Physicians and Surgeons in New York . He then immigrated to Israel , and pursued post-doctoral studies at the Hebrew University examining the neurobiology of cockroach escape and  the ontogeny of the dorsal root ganglia of the chick before joining the faculty at Bar-Ilan.

The focus of research in his laboratory has been the development of the peripheral nervous system using the chick embryo as a model. From 1995-2000, his research on the characterization and attempted rescue of a DRG that degenerates in normal embryonic development was supported by the FDI.