New Technique for Dopamine Cell Replacement in PARKINSON’S DISEASE



New Technique for Dopamine Cell Replacement in PARKINSON’S DISEASE


Love those Italians…. they excel in fashion design and make the best designer shoes!  Now they have taken design to the cellular level and are creating designer drugs for designer receptors on those cells.  They call it DREADD (designer receptor exclusively activated by designer drug.  But this is really serious science.


Cell transplantation in PARKINSON’S DISEASE, while in theory, sounds very plausible, in practice has yielded mixed results with the development of serious dyskinesias or even tumors being a major problem. Because it is a particular type of neuronal cell that is affected in PARKINSON’S DISEASE, cell therapy with dopamine producing cells could yield a potential therapeutic treatment.  If dopamine producing cells could be developed, transplanted and become effective and efficient producers of dopamine, the troublesome motor symptoms that plague people with PARKINSON’S could be banished.


Embryonic stem cells or induced pluripotent stem cells have been developed from both mouse and human cells and have been somewhat effective in alleviating motor symptoms when transplanted into animal models of PARKINSON’S DISEASE.  But if the differentiation from stem cell to dopamine producing cell is not well controlled, tumors can develop.  Cells developed from human fibroblasts can be induced to become neurons, but are more difficult to produce, with more opportunity for potential error.  Much stem cell technology exists only in petri dishes, and the degree to which these reprogrammed cells would be functional or stable when transplanted into living models is not yet known. For modified cells to be transplanted and become effective a system needs to be developed that will allow the transplanted cells to be monitored and modulated to serve the physiological environment into which they are introduced.


Previous studies have shown that only dopamine neurons from the mid brain region were successful in reversing motor function in lesioned rats.  This team developed an induced dopaminergic neuron (iDA) from fibroblast, so the challenge was to see if it could be as effective as mid brain dopamine neurons.  The grafted iDA neurons did improve the motor function of the animals, but not as well as native embryonic DA neurons.  Stereological cell counting showed that there were as many surviving iDA cells as there were native DA cells and this lead to the idea that iDA neurons were less functional intrinsically. The team believes that an improved method for generating better quality induced pluripotent stem cells from the fibroblasts will result in more uniformly expressing iDA neurons.


To measure the integration of the iDA neurons into the host environment, they used the DREADD technology.  This technology allows the addition of a uniquely designed receptor that permits a specific interaction with a pharmacological drug to manipulate the activity of the re-programmed neuron.  It thus enforces a sort of “remote control” over the transplanted neuron to enhance its effects in living animals. This method may offer a better approach to cell replacement therapy by combining an external, pharmacological agent with the transplanted re-programmed neurons to respond to the physiological needs and requirements of the recipient.

This research study was done by a large team of researchers under the direction of Vania Broccoli, Ph.D. who is a developmental neurologist at the Hospital San Rafaele in Milan, Italy.  It will be published in the Journal of Clinical Investigation on July 1, 2013.


Broccoli, V. et al; Remote control of induced dopaminergic neurons in parkinsonian rats; J Clin Invest. 2014;124(7):3215-3229. doi:10.1172/JCI74664



Review by Marcia McCall

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