This proving iPSCs are a better option because they have similar findings as the mouse model with more of an advantage linking to the human patients since these iPSCs were from human patients with the disease. Overall the end goal is to find a drug that slows the progression or stops the neurodegeneration in humans for this specific disease and being able to test the drugs out in human cells rather than animal cells would have more advantages.
Another important aspect of iPSCs is the number of cells obtained is more than what can be gathered from using a mouse model (1). The number of cells grown is a key factor that leads into using a drug screening and the best part is being able to test small amounts of drugs with large libraries of 3,000 different kinds of compounds (1), which testing many drugs needs an effective way to obtain many cells and can be done with iPSCs. In addition to that, once certain drugs are shown to be effective, also called hits, they can be selected for more in-depth screenings which can also be done on primary cells as well (5). This is very helpful in the fact that the certain drugs can be tested in different types of cells such as Purkinje and dorsal root ganglions since motor neurons are not the only cell type that gets affected by this disease and to test the drugs on them would help give more insight on the drugs affect.
Drug screenings are also highly cost-efficient where performing smaller tests on multiple compounds can save more money in the long run (5). Figure 2 is a great depiction of how the flow of drug screening can lead to the end goal (5). The timeline shows how in the beginning, the drug screening is less expensive than the end experiments and once learning more about the hits that were obtained from the first screen then it leads into refinements and optimizing only if the results continues to provide beneficial (5). This is where Gilmore et al.’s lab (1) is heading towards with the iPSCs after completions of testing the 384-well plates. In addition, other recent articles such as Chuang et al (2) and Lariosa-Willingham et al (4), discuss the use of drug screening showing this is an acceptable test that is currently still being used in research.
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