Working Towards Replacement Neurons for Parkinson's Disease

Parkinson's researchers were among the first to earnestly attempt to create a specific cell type for transplant, and have continued to work at this. The obvious symptoms of Parkinson's are caused by the progressive loss of a thin population of dopamine-producing neurons, and therefore a way of replacing those specialist cells wholesale would be a way to temporarily reverse the course of the disease - perhaps for years or even decades in the best case. Thus these researchers now make up one of the more experienced scientific communities involved in cell therapy research, and can be counted on to rapidly pick up promising new developments in the control and reprogramming of cells. In past years, the focus has been on producing cells for transplant:

Once researchers have demonstrated control over cellular reprogramming, the ability to turn one cell type into another by providing suitable signals, the focus starts to shift away from transplants and on to reprogramming cells in situ: instructing the body - or the brain in this case - to directly produce more of the needed cell type. Here's an example for Parkinson's disease (PD):

In the first step towards a direct cell replacement therapy for Parkinson's, the team reprogrammed astrocytes to dopaminergic neurons using three transcription factors - ASCL1, LMX1B, and NURR1 - delivered with a lentiviral vector. The process is efficient, with about 18 percent of cells expressing markers of dopaminergic neurons after two weeks. The next closest conversion efficiency is approximately 9 percent, which was reported in another study. The dopamine-producing neurons derived from astrocytes showed gene expression patterns and electrophysiolgical properties of midbrain dopaminergic neurons, and released dopamine when their cell membranes were depolarized.

The Penn team is now working to see if the same reprogramming process that converts astrocytes to dopamine-producing neurons in a dish can also work within a living brain - experiments will soon be underway using gene therapy vectors to deliver the reprogramming factors directly to astrocytes in a monkey model of PD.

I'll go out on a limb and suggest that transplants are probably not the be-all and end end-all future of tissue engineering. By the time the 2020s roll around, I'd guess that most of the new therapies moving into US trials and clinical use overseas will be based on delivering increasingly precise and targeted reprogramming instructions into the body rather than introducing new cells or taking the patient's cells and working with them outside the body to produce tissue for transplantation.

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