Drug Discovery for Parkinson's Disease
The progressive loss of neurons in the brain of Parkinson’s patients is slow yet inexorable. So far, there are no drugs that can halt this insidious process. Researchers at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have now managed to grow the types of neurons affected starting from neuronal stem cells in a three-dimensional cell culture system. A release from the university reports that the scientists working with Dr. Ronan Fleming of the LCSB research group Systems Biochemistry are confident this system could greatly facilitate the continuing search for therapeutic agents in future as it models the natural conditions in the brain more realistically than other systems available so far. It is also significantly cheaper to employ in the laboratory. The results were recently published in the journal Lab on a Chip.
Parkinson’s disease is characterized in particular by the death of dopamine-producing neurons in the Substantia nigra of the midbrain. It is already possible to grow these dopaminergic neurons in cell cultures. The release quotes group leader Fleming as saying, “But most such cell cultures are two-dimensional, with the cells growing along the base of a petri dish, for example. Instead, we have the neurons grow in a gel that yields a far better model of their natural, three-dimensional environment.”
As the starting point for cultivating the target neurons, the scientists use ordinary skin cells. They convert these through conventional methods into induced pluripotent stem cells, or iPSCs for short. For the development of this technology Japanese scientist Shinya Yamanaka was awarded the Nobel Prize for Physiology or Medicine in 2012 together with John Gurdon. “By adding suitable growth factors, the iPSCs can then be converted in a second step into neural stem cells,” says Prof. Jens Schwamborn, head of the LCSB research group Developmental & Cellular Biology, which is responsible for the differentiation of the cells. “These are the starting cells we use in the microfluidic culture.”
The researchers first mix the cells with a liquid, which they then fill into little test vessels called bioreactors. “You can imagine such a bioreactor as a tunnel separated down the middle by a flat barrier,” LCSB researcher Edinson Lucumi Moreno, first author of the study, explains. “One side of the tunnel we load the liquid with the cells, where it hardens into a gel under controlled temperatures. The other side we load with a medium to which we can add nutrients and substances for further differentiation of the neuronal stem cells as required.”