Parkinson’s disease (PD) is a degenerative disorder affecting the central nerve system. A person with Parkinson’s disease may develop muscular rigidity, tremors, and altered speech patterns. The person may also have problems using language and lose higher cognitive functions. PD may cause a person to move very slowly (bradykinesia) and may cause loss of balance. The disease is progressive and chronic. PD is not fatal, but eventually severe muscular problems may cause pneumonia, choking, and falls which may result in death. PD affects approximately 150 out of every 100,000 Caucasian individuals, and is slightly less prevalent among African-Americans.
Parkinson’s disease is caused by decreased activity of dopamine (DA)-secreting nerve cells located in the substantia nigra (“black substance”) of the brain. DA is a neurotransmitter involved in the regulation of muscular activity as well as various neuropsychiatric functions including cognition and behavior. A common medical treatment for PD is L-Dopa which is converted into DA by dopaminergic neurons in the substantia nigra. Administration of L-Dopa attempts to replace the body’s supply of DA. The drug is not an optimal therapy – only a small percentage is converted to DA and the drug causes many side-effects.
PD is an ideal candidate for stem cell treatment. Brilliant research by Wernig et al.1 (conducted in the Jaenisch laboratory at the Whitehead Institute for Biomedical Research) demonstrated successful treatment of PD in adult rats using neurons derived from stem cells. These authors derived iPS cells by reprogramming rat connective tissue cells. The stem cells were then transformed into neuronal cell types and transplanted into the brains of adult rat models of PD. The nerve cells were successfully transplanted and led to functional recovery in eight of nine rats. Importantly, no cancers that might have been caused by the transplants were detected up to eight weeks following transplantation.
An additional remarkable study was reported recently by Zhou et al.2 at the Harvard Stem Cell Institute. Using an in vivo approach in adult mice, this team directly converted mouse pancreatic exocrine cells into pancreatic endocrine ?-cells. The team used an adenovirus to transfect the exocrine cells with a specific combination of transcription factors, effectively reprogramming the exocrine cells into endocrine ?-cells. This stunning breakthrough demonstrates that it is possible in certain circumstances to avoid the necessity of reprogramming a cell to an embryonic pluripotent state. Zhou et al showed that transdifferentiation is possible by using a cocktail of lineage-specific transcription factors.
Much work is needed to be done, of course. Yet the work of both these research teams points to exciting new possibilities for treatment of these devastating diseases.
The field of regenerative medicine is progressing at an astonishing rate. Hallowed concepts of embryology and development are being revised, practically on-the-fly, yearly if not monthly. We are living in very exciting times.
Tags: biomedical research